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sonic hedgehog promotes rod photoreceptor differentiation in mammalian retinal cells in vitro.the hedgehog gene family encodes secreted proteins important in many developmental patterning events in both vertebrates and invertebrates. in the drosophila eye disk, hedgehog controls the progression of photoreceptor differentiation in the morphogenetic furrow. to investigate whether hedgehog proteins are also involved in the development of the vertebrate retina at stages of photoreceptor differentiation, we analyzed expression of the three known vertebrate hedgehog genes. we found that sonic ...19979236238
regional distribution of sonic hedgehog, patched, and smoothened mrna in the adult rat brain.in vertebrates, sonic hedgehog (shh), desert hedgehog (dhh), and indian hedgehog (ihh) genes encode a family of morphogen proteins that are implicated in a wide range of signaling activities, particularly during embryonic development. these secreted proteins are proposed to mediate their effects on target cells by interacting with their putative receptor, patched (ptc), and with a seven-pass transmembrane protein, smoothened (smo). however, the roles that these signaling molecules may play in ad ...19989489757
characterization of two patched receptors for the vertebrate hedgehog protein family.the multitransmembrane protein patched (ptch) is the receptor for sonic hedgehog (shh), a secreted molecule implicated in the formation of embryonic structures and in tumorigenesis. current models suggest that binding of shh to ptch prevents the normal inhibition of the seven-transmembrane-protein smoothened (smo) by ptch. according to this model, the inhibition of smo signaling is relieved after mutational inactivation of ptch in the basal cell nevus syndrome. recently, ptch2, a molecule with s ...19989811851
schwann cell-derived desert hedgehog controls the development of peripheral nerve sheaths.we show that schwann cell-derived desert hedgehog (dhh) signals the formation of the connective tissue sheath around peripheral nerves. mrnas for dhh and its receptor patched (ptc) are expressed in schwann cells and perineural mesenchyme, respectively. in dhh-/- mice, epineurial collagen is reduced, while the perineurium is thin and disorganized, has patchy basal lamina, and fails to express connexin 43. perineurial tight junctions are abnormal and allow the passage of proteins and neutrophils. ...199910482238
assignment of human desert hedgehog gene (dhh) to chromosome band 12q13.1 by in situ hybridization. 199910640830
assignment of desert hedgehog (dhh) to human chromosome bands 12q12-->q13.1 by in situ hybridization. 200010773676
a novel mutation of desert hedgehog in a patient with 46,xy partial gonadal dysgenesis accompanied by minifascicular neuropathy.we describe a patient with 46,xy partial gonadal dysgenesis (pgd) who presented with polyneuropathy. sural nerve pathology revealed peculiar findings characterized by extensive minifascicular formation within the endoneurium and with a decreased density of myelinated fibers. we found, in the patient, a homozygous missense mutation (atg-->acg) at the initiating codon in exon 1 of the desert hedgehog (dhh) gene, which predicts a failure of translation of the gene. the same heterozygous mutation wa ...200011017805
desert hedgehog (dhh) gene is required in the mouse testis for formation of adult-type leydig cells and normal development of peritubular cells and seminiferous tubules.testes from adult and prepubertal mice lacking the desert hedgehog (dhh:) gene were examined in order to describe further the role of dhh in spermatogenesis because, in a previous report, dhh:-null male mice were shown to be sterile. dhh is a signaling molecule expressed by sertoli cells. its receptor, patched (ptc), has been previously localized to leydig cells and is herein described as being localized also to peritubular cells. two phenotypes of the mice were observed: masculinized (7.5% of d ...200011090455
hedgehog signaling regulation of insulin production by pancreatic beta-cells.hedgehogs (hhs) are intercellular signaling molecules that regulate tissue patterning in mammalian development. mammalian hhs include sonic hedgehog (shh), indian hedgehog (ihh), and desert hedgehog (dhh). the absence of shh expression is required for the early development of the endocrine and exocrine pancreas, but whether hh signaling functions in the fully developed adult endocrine pancreas is unknown. here we report that hhs ihh and dhh and their receptors patched (ptc) and smoothened are ex ...200011118005
comparative biological responses to human sonic, indian, and desert hedgehog.a comprehensive comparison of sonic (shh), indian (ihh), and desert (dhh) hedgehog biological activities has not previously been undertaken. to test whether the three higher vertebrate hh proteins have distinct biological properties, we compared recombinant forms of the n-terminal domains of human shh, ihh, and dhh in a variety of cell-based and tissue explant assays in which their activities could be assessed at a range of concentrations. while we observed that the proteins were similar in thei ...200111472839
a developmental study of the desert hedgehog-null mouse testis.desert hedgehog (dhh) is a cell-signaling molecule that was first discovered in drosophila. a unique testicular phenotype has been described in neonatal and adult dhh-null animals that includes anastomotic seminiferous tubules, pertitubular cell abnormalities, and absence of adult-type leydig cells. in the present study, we addressed the developmental basis for the abnormalities previously described for the adult dhh-null phenotype. the source of dhh is the sertoli cell, and receptors are locali ...200111673255
gli1 localization in the germinal epithelial cells alternates between cytoplasm and nucleus: upregulation in transgenic mice blocks spermatogenesis in pachytene.the zinc finger transcription factor gli1 is the mediator of signaling by members of the hedgehog (hh) family. male mice in which desert hedgehog (dhh), an hh homologue expressed in sertoli cells of the testis, was knocked out are sterile, suggesting that the dhh/gli1 pathway plays a role in spermatogenesis. using an antiserum raised against human gli1, we found that during the first round of spermatogenesis, gli1 expression is initially cytoplasmic, then shifts to the nuclei of sertoli and germ ...200111717126
scip/oct-6, krox-20, and desert hedgehog mrna expression during cns remyelination by transplanted olfactory ensheathing cells.olfactory ensheathing cells (oecs), although having a separate developmental origin to schwann cells, are able to generate myelin sheaths following transplantation into areas of cns demyelination that are remarkably similar to those made by schwann cells. the transcriptional control of schwann cell myelination has been well documented, in particular the role of scip/oct-6 and krox-20. it is not known, however, whether these transcription factors are also expressed when oecs assume a myelinating ...200111746771
schwann cells as regulators of nerve development.myelinating and non-myelinating schwann cells of peripheral nerves are derived from the neural crest via an intermediate cell type, the schwann cell precursor [k.r. jessen, a. brennan, l. morgan, r. mirsky, a. kent, y. hashimoto, j. gavrilovic. the schwann cell precursor and its fate: a study of cell death and differentiation during gliogenesis in rat embryonic nerves, neuron 12 (1994) 509-527]. the survival and maturation of schwann cell precursors is controlled by a neuronally derived signal, ...200211755779
minifascicular neuropathy: a new concept of the human disease caused by desert hedgehog gene mutation.we recently found a patient with 46,xy partial gonadal dysgenesis who presented with polyneuropathy. sural nerve pathology revealed peculiar findings characterized by extensive minifascicular formation and with a decreased density of myelinated fibers. we found in the patient, a homozygous missense mutation at the initiating codon in exon 1 of the desert hedgehog (dhh) gene, which predicts a failure of translation of the gene. these data demonstrate that dhh is a key molecule in both male gonada ...200211990454
desert hedgehog/patched 1 signaling specifies fetal leydig cell fate in testis organogenesis.establishment of the steroid-producing leydig cell lineage is an event downstream of sry that is critical for masculinization of mammalian embryos. neither the origin of fetal leydig cell precursors nor the signaling pathway that specifies the leydig cell lineage is known. based on the sex-specific expression patterns of desert hedgehog (dhh) and its receptor patched 1 (ptch1) in xy gonads, we investigated the potential role of dhh/ptch1 signaling in the origin and specification of fetal leydig ...200212050120
signals that determine schwann cell identity.while the signals that direct neural crest cells to choose the glial lineage and generate schwann cell precursors are still obscure, studies both in vivo and in vitro indicate that the survival and differentiation of these cells to form schwann cells is regulated by at least two signals, neuregulin-1 and endothelin. we know little about the signals that cause some immature schwann cells to choose myelin differentiation, while other cells form non-myelinating cells. three transcription factors, s ...200212090403
comparison of hedgehog and patched-1 protein expression in the cranial sutures of craniosynostotic and wild-type rabbits.craniosynostosis is characterized by premature fusion of the cranial sutures. at the molecular level, mutations in homeobox genes, transcription factors, and growth factor receptors have been implicated in the pathogenesis of this disorder, but the specific etiologic pathways have not yet been elucidated. to further study the molecular biology behind craniosynostosis, perisutural tissues in a unique rabbit model with congenital delayed-onset coronal craniosynostosis were examined for the presenc ...200212142670
changes in the protein expression of hedgehog and patched-1 in perisutural tissues induced by cranial distraction.with the modern emphasis on minimally invasive therapies, the concept of distraction is being applied in the treatment of craniosynostosis. although specific genetic mutations have been identified in craniosynostotic patients, changes in the gene expression induced by cranial distraction have not yet been explored. the effects of cranial distraction on hedgehog and patched-1 expression were evaluated in a rabbit model for craniosynostosis. rabbits (n = 8) were divided into four groups: affected ...200212142671
a possible paracrine hedgehog signalling pathway in neurofibromas from patients with neurofibromatosis type 1.hedgehogs (hhs) and their receptors are involved in organ development as well as in tumorigenesis observed in basal cell carcinoma. among hhs, desert hedgehog secreted from schwann cells mediates the formation of peripheral nerve sheaths. however, there has been no study on the role of hhs and their receptors in tumorigenesis of neurofibromas in neurofibromatosis type 1 (nf1).200312588389
therapeutic efficacy of sonic hedgehog protein in experimental diabetic neuropathy.hedgehog proteins modulate development and patterning of the embryonic nervous system. as expression of desert hedgehog and the hedgehog receptor, patched-1, persist in the postnatal and adult peripheral nerves, the hedgehog pathway may have a role in maturation and maintenance of the peripheral nervous system in normal and disease states. we measured desert hedgehog expression in the peripheral nerve of maturing diabetic rats and found that diabetes caused a significant reduction in desert hedg ...200312588889
a novel function for hedgehog signalling in retinal pigment epithelium differentiation.sonic hedgehog is involved in eye field separation along the proximodistal axis. we show that hh signalling continues to be important in defining aspects of the proximodistal axis as the optic vesicle and optic cup mature. we show that two other hedgehog proteins, banded hedgehog and cephalic hedgehog, related to the mouse indian hedgehog and desert hedgehog, respectively, are strongly expressed in the central retinal pigment epithelium but excluded from the peripheral pigment epithelium surroun ...200312620982
a tissue-specific knockout reveals that gata1 is not essential for sertoli cell function in the mouse.the transcription factor gata1 is essential for the development of erythroid cells. consequently, gata1 null mutants die in utero due to severe anaemia. outside the haematopoietic system, gata1 is only expressed in the sertoli cells of the testis. to elucidate the function of gata1 in the testis, we made a sertoli cell-specific knockout of the gata1 gene in the mouse. we deleted a normally functioning 'floxed' gata1 gene in pre-sertoli cells in vivo through the expression of cre from a transgene ...200312954777
characterization of kif7 gene in silico.sonic hedgehog (shh), indian hedgehog (ihh) and desert hedgehog (dhh) are hedgehog family ligands, which play key roles in embryogenesis and carcinogenesis, especially in pancreatic cancer and gastric cancer. drosophila costal-2 (cos2) is a hedgehog signaling regulator, interacting with smoothened (smo), cubitus interruptus (ci), fused (fu) and microtubule. kif27 is one of the mammalian orthologs for drosophila cos2. kif7 gene is the paralog of kif27 gene; however, complete coding sequence (cds) ...200415547730
identification and characterization of rat desert hedgehog and indian hedgehog genes in silico.sonic hedgehog (shh), desert hedgehog (dhh) and indian hedgehog (ihh) bind to patched family receptors (ptch1 and ptch2) to transduce signals to gli1, gli2 and gli3. gli family transcription factors then activate transcription of hedgehog target genes, such as foxe1 and foxm1 encoding forkhead-box transcription factors. hedgehog signaling pathway plays a pivotal role in a variety of human tumors, such as gastric cancer, pancreatic cancer, colorectal cancer, breast cancer, prostate cancer, basal ...200515645142
hedgehog signaling in mouse ovary: indian hedgehog and desert hedgehog from granulosa cells induce target gene expression in developing theca cells.follicle development in the mammalian ovary requires interactions among the oocyte, granulosa cells, and theca cells, coordinating gametogenesis and steroidogenesis. here we show that granulosa cells of growing follicles in mouse ovary act as a source of hedgehog signaling. expression of indian hedgehog and desert hedgehog mrnas initiates in granulosa cells at the primary follicle stage, and we find induced expression of the hedgehog target genes ptch1 and gli1, in the surrounding pre-theca cell ...200515878962
comparative genomics on sonic hedgehog orthologs.sonic hedgehog (shh), indian hedgehog (ihh), and desert hedgehog (dhh) are key molecules for the integrome network in oncology and regenerative medicine. soluble hedgehog ligands bind to patched receptor to activate smoothened seven-transmembrane receptor with frizzled domain. kif27 and kif7 are human homologs of drosophila costal-2 (cos2), associating with smoothened, gli homolog, fused, and microtubule. smoothened activation leads to gli1, gli2, or gli3-dependent transcription of hedgehog targ ...200516142377
desert hedgehog-patched 2 expression in peripheral nerves during wallerian degeneration and regeneration.hedgehog proteins are important in the development of the nervous system. as desert hedgehog (dhh) is involved in the development of peripheral nerves and is expressed in adult nerves, it may play a role in the maintenance of adult nerves and degeneration and regeneration after injury. we firstly investigated the dhh-receptors, which are expressed in mouse adult nerves. the dhh receptor patched(ptc)2 was detected in adult sciatic nerves using rt-pcr, however, ptc1 was undetectable under the same ...200616329124
the foetal leydig cell-- differentiation, function and regulation.the foetal leydig cell population arises shortly after testicular differentiation at around 12.5 dpc in the mouse and 6 weeks in the human. these cells function, primarily, to produce androgens which are essential for masculinization of the foetus. the origin of the foetal leydig cells remains uncertain but it has been suggested that adrenocortical cells and foetal leydig cells may share a common origin in an adreno-genital primordium. studies in the mouse are beginning to identify factors such ...200616466528
hedgehog signaling in the normal and diseased pancreas.the hedgehog (hh) family of genes, sonic hedgehog (shh), indian hedgehog (ihh), and desert hedgehog (dhh) encode signaling molecules that regulate multiple functions during organ development and in adult tissues. altered hedgehog signaling has been implicated in disturbed organ development as well as in different degenerative and neoplastic human diseases. hedgehog signaling plays an important role in determination the fate of the mesoderm of the gut tube, as well as in early pancreatic developm ...200616552330
sprouty2 is involved in male sex organogenesis by controlling fibroblast growth factor 9-induced mesonephric cell migration to the developing testis.fibroblast growth factor 9 (fgf9) signal has a role in organogenesis of the mammalian testis by controlling migration of mesonephric cells to the xy gonad, but neither it nor the fgf receptors is expressed sex-specifically. of the sprouty genes encoding antagonists of receptor tyrosine kinases including fgfr, msprouty2 expression was confined to the developing testis and mesonephros. gain of sprouty2 function in the male genital ridge and mesonephros malformed the vas deferens and epididymis, an ...200616675530
the structural and functional integrity of peripheral nerves depends on the glial-derived signal desert hedgehog.we show that desert hedgehog (dhh), a signaling molecule expressed by schwann cells, is essential for the structural and functional integrity of the peripheral nerve. dhh-null nerves display multiple abnormalities that affect myelinating and nonmyelinating schwann cells, axons, and vasculature and immune cells. myelinated fibers of these mice have a significantly increased (more than two times) number of schmidt-lanterman incisures (slis), and connexin 29, a molecular component of slis, is stron ...200616763045
hedgehog signal activation in gastric pit cell and in diffuse-type gastric cancer.sonic hedgehog (shh) and indian hedgehog (ihh) have cell-specific actions in some organs. only shh has been shown to regulate parietal cell differentiation. this study examined whether shh, 2 other ligands ihh and desert hedgehog, and receptors or downstream targets are expressed in normal gastric epithelium or in intestinal and diffuse-type gastric cancers. the effects of a hedgehog (hh) inhibitor, cyclopamine, were assessed in primary gastric epithelium cultures and gastric cancer cell lines.200616831586
in vivo detection of egr2 binding to target genes during peripheral nerve myelination.egr2/krox20 is a zinc finger transactivator that regulates a diverse array of genes required for peripheral nerve myelination. although several studies have elucidated the egr2-regulated gene network, it is not clear if egr2 regulates its target genes directly or indirectly through induction of other transactivators. moreover, very few egr2 binding sites have been identified in regulatory elements of myelin genes. to address this issue, we have successfully adapted chromatin immunoprecipitation ...200616923174
elevated anxiety-like and depressive behavior in desert hedgehog knockout male mice.to investigate the functional role of desert hedgehog (dhh) gene in the nervous system, we examined motor, sensory, learning and memory functions as well as mood in dhh knockout (ko) mice. dhh ko male mice exhibited prolonged immobility time compared with wild-type male mice in the forced swimming test, and showed enhanced inhibition in the vogel's conflict model. these findings suggest that dhh ko male mice exhibited enhanced anxiety and depressive behavior compared with wild-type male mice. in ...200616952407
hedgehog signaling pathway and gastrointestinal stem cell signaling network (review).hedgehog, bmp/tgfbeta, fgf, wnt and notch signaling pathways constitute the stem cell signaling network, which plays a key role in a variety of processes, such as embryogenesis, maintenance of adult tissue homeostasis, tissue repair during chronic persistent inflammation, and carcinogenesis. sonic hedgehog (shh), indian hedgehog (ihh) and desert hedgehog (dhh) bind to ptch1/ptch or ptch2 receptor to release smoothened (smo) signal transducer from patched-dependent suppression. smo then activates ...200617089004
the expression of hedgehog genes (ihh, dhh) and hedgehog target genes (ptc1, gli1, coup-tfii) is affected by estrogenic stimuli in the uterus of immature female rats.the objective of this study was to investigate the effects of estrogen receptor (er) agonists and an er antagonist on the expression of hedgehog genes (indian hedgehog: ihh; desert hedgehog: dhh) and hedgehog target genes (patched 1: ptc1; glioma-associated oncogene homolog 1: gli1; chicken ovalbumin upstream promoter transcription factor ii: coup-tfii) in the rat uterus. immature female rats were administered once with 17alpha-ethynyl estradiol (ee, an er agonist), propyl pyrazole triole (ppt, ...200617109907
sonic and desert hedgehog signaling in human fetal prostate development.hedgehog signaling is thought to play an important role in rodent prostate organogenesis and morphogenesis. however, the role of this signaling pathway in human fetal prostate development has not been investigated.200717342747
distinct roles for steroidogenic factor 1 and desert hedgehog pathways in fetal and adult leydig cell development.testicular leydig cells produce testosterone and provide the hormonal environment required for male virilization and spermatogenesis. in utero, fetal leydig cells (flcs) are necessary for the development of the wolffian duct and male external genitalia. steroidogenic factor 1 (sf1) is a transcriptional regulator of hormone biosynthesis genes, thus serving a central role in the leydig cell. desert hedgehog (dhh), a sertoli cell product, specifies the flc lineage in the primordial gonad through a ...200717495005
sonic hedgehog regulates hes1 through a novel mechanism that is independent of canonical notch pathway signalling.aberrant regulation of signalling mechanisms that normally orchestrate embryonic development, such as the hedgehog, wnt and notch pathways, is a common feature of tumorigenesis. in order to better understand the neoplastic events mediated by hedgehog signalling, we identified over 200 genes regulated by sonic hedgehog in multipotent mesodermal cells. widespread crosstalk with other developmental signalling pathways is evident, suggesting a complex network of interactions that challenges the ofte ...200817873912
maternal smoking during pregnancy specifically reduces human fetal desert hedgehog gene expression during testis development.maternal cigarette smoking during gestation increases cryptorchidism and hypospadias and reduces testis size and fertility in sons by unknown mechanisms.200818000085
purifying the hedgehog protein and its variants.the purification of recombinant versions of the n-terminal signaling fragment of sonic hedgehog (shhn) from e. coli, hi-5 insect cells, yeast, and mammalian cell sources reveals diverse post-translational modifications that affect the potency of the purified protein. modifications to the n-terminal cysteine with fatty acyl groups results in significant increases in potency, up to 100-fold, when compared with the unmodified protein. proteolytic clipping at sites near the n-terminus results in ina ...200718025709
leydig cell re-generation and expression of cell signaling molecules in the germ cell-free testis.leydig cells in the rat testis can be specifically ablated with ethane dimethane sulfonate (eds) and will subsequently re-generate. in this study, we have characterized leydig cell re-generation and expression of selected cell-signaling molecules in a germ cell-free model of eds action. this model offers the advantage that re-generation occurs on a stable background without confounding changes from the regressing and repopulating germ cell population. adult rats were treated with busulfan to rem ...200818502897
purification and bioassay of hedgehog ligands for the study of cell death and survival.the hedgehog (hh) family of secreted ligands-composed of sonic hedgehog (shh), indian hedgehog (ihh), and desert hedgehog (dhh)-possesses many roles during embryonic development, adult homeostasis, and cancer. the specific functions of the hh proteins are intertwined with their requirement as survival factors in hh-responsive cells. however, studies designed to dissect the anti-apoptotic role of hhs have been hindered by the lack of simple approaches to purify large quantities of recombinant lig ...200818603123
expression of hedgehog family genes in the rat uterus during early pregnancy.hedgehog (hh) plays a pivotal role in various tissues during embryonic development, tissue homeostasis and tumorigenesis. in mammals, hh exists in three homologs: desert hedgehog (dhh), indian hedgehog (ihh) and sonic hedgehog (shh). in this study, we cloned full-length cdnas encoding dhh and ihh from the rat uterus. their amino acid sequences have a high homology with those of the mouse and human. in addition, the changes of hh gene expression in the rat uterus during early pregnancy were analy ...200818612197
antiandrogen exposure in utero disrupts expression of desert hedgehog and insulin-like factor 3 in the developing fetal rat testis.testicular development is an androgen-dependent process, and fetal exposure to antiandrogens disrupts male sexual differentiation. a variety of testicular disorders may result from impaired development of fetal leydig and sertoli cells. we hypothesized that antiandrogenic exposure during fetal development interferes with desert hedgehog (dhh) signaling in the testis and results in impaired leydig cell differentiation. fetal rats were exposed in utero to the antiandrogen flutamide from 10.5 d pos ...200918772241
activation of the hedgehog pathway in the mouse fetal ovary leads to ectopic appearance of fetal leydig cells and female pseudohermaphroditism.proper cell fate determination in mammalian gonads is critical for the establishment of sexual identity. the hedgehog (hh) pathway has been implicated in cell fate decision for various organs, including gonads. desert hedgehog (dhh), one of the three mammalian hh genes, has been implicated with other genes in the establishment of mouse fetal leydig cells. to investigate whether hh alone is sufficient to induce fetal leydig cell differentiation, we ectopically activated the hh pathway in steroido ...200919268447
hedgehog signaling is involved in differentiation of normal colonic tissue rather than in tumor proliferation.the hedgehog (hh) pathway is a main regulation cascade in embryonic differentiation. it is also present in adult tissues and unusual expression has been associated with formation of benign and malignant lesions. we examined the presence of the hedgehog pathway in normal and pathological human colon tissue. components investigated include sonic (shh), indian (ihh), and desert hedgehog (dhh), gli1, gli2, gli3, and patched (ptch). pathological tissue samples comprised 23 benign and 20 malignant les ...200919280222
the role of hedgehog signaling during gastric regeneration.hedgehog signaling plays critical roles during embryonic development. it is also involved in tissue regeneration and carcinogenesis in various adult tissues. moreover, it regulates the maintenance of cancer stem cells and adult stem cells. although hedgehog signaling is important in gastric carcinogenesis, its role in gastric regeneration has not been previously examined. in the present study, we evaluated the expression and roles of hedgehog signaling during gastric regeneration.200919291354
expression of patched-1 and smoothened in testicular meiotic and post-meiotic cells.desert hedgehog (dhh) signaling plays an essential role in the normal development of the testis and in the process of spermatogenesis. little is known about the involvement in spermatogenesis of the prototypic member of the family, ptc1, which acts to suppress hedgehog signaling through smoothened (smo). here, we have examined the expression of ptc1, smo, and dhh in mouse and rat seminiferous epithelium. our findings demonstrate that ptc1 and smo are expressed by primary spermatocytes and by rou ...200919484749
structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein hhip.hedgehog (hh) morphogens have fundamental roles in development, whereas dysregulation of hh signaling leads to disease. multiple cell-surface receptors are responsible for transducing and/or regulating hh signals. among these, the hedgehog-interacting protein (hhip) is a highly conserved, vertebrate-specific inhibitor of hh signaling. we have solved a series of crystal structures for the human hhip ectodomain and desert hedgehog (dhh) in isolation, as well as hhip in complex with dhh (hhip-dhh) ...200919561611
hedgehog proteins activate pro-angiogenic responses in endothelial cells through non-canonical signaling pathways.the hedgehog (hh) pathway orchestrates developmental and homeostatic angiogenesis. the three hh isoforms--sonic hedgehog (shh), indian hedgehog (ihh) and desert hedgehog (dhh)--signal through patched-1 (ptch1) and smoothened (smo), to activate the gli transcription factors with a characteristic rank of potency (shh >> ihh > dhh). to dissect the mechanisms through which hh proteins promote angiogenesis, we analyzed processes inherent to vessel formation in endothelial cells. we found that none of ...201020081366
establishment of long-term monolayer cultures of somatic cells from human fetal testes and expansion of peritubular myoid cells in the presence of androgen.the somatic (sertoli cell (sc), leydig cell (lc), and peritubular myoid (ptm) cell) cells play key roles in development of the fetal testis. we established monolayer cultures from second trimester human testes and investigated the pattern of expression of cell-lineage characteristic mrnas. expression of some sc-associated genes (sry, sox9, wt1, gata4, and sf1) was detectable up to and including passage 3 (p3), while others (anti-müllerian hormone; desert hedgehog) present prior to dissociation w ...201020089665
origin, development and regulation of human leydig cells.sex steroids are crucial regulators of sexual differentiation and the proper development of secondary sex characteristics and patterns of sexual behavior. since leydig cells are the primary major producers of these steroid hormones, maintenance of the normal functions of these cells determines the reproductive capacity and fertility of males. the present minireview discusses recent findings concerning endocrine and paracrine regulation of the proliferation, differentiation and involution of huma ...201020190545
human plasma very low density lipoprotein carries indian hedgehog.hedgehog is one of the major morphogens and fulfils critical functions in both the development and maintenance of the vasculature. hedgehog is highly hydrophobic and its diffusion toward target tissues remains only partly understood. in drosophila, hedgehog transport via lipophorins is relevant for development, but neither the presence nor a function for a mammalian hedgehog carried by human plasma lipoproteins has been established. we investigated the presence of hedgehog on lipoprotein particl ...201020839884
effects of low intensity pulsed ultrasound on rat schwann cells metabolism.the effects of low intensity pulsed ultrasound to tenocytes and osteocytes are well understood and applied clinically. however, its effects on cultured schwann cells are still not well elucidated. this study was designed to elucidate the effects of low intensity pulsed ultrasound on cultured schwann cells and their possible molecular mechanism. schwann cells were harvested from sciatic nerves of 3-day-old sprague-dawley rats. low intensity pulsed ultrasound stimulator (frequency: 1 mhz, duration ...201020946299
a missense mutation of the dhh gene is associated with male pseudohermaphroditic rats showing impaired leydig cell development.development of the male gonads is a complex process with interaction of various cells in the gonads including germ, sertoli, leydig, and myoid cells. tf is a mutant rat strain showing male pseudohermaphroditism, with agenesis of leydig cells and androgen deficiency controlled by an autosomal single recessive gene (mp). the mp locus was mapped on the distal region of rat chromosome 7 by linkage analysis, but the gene responsible for the mp mutation has not been identified. in this study, we perfo ...201021062903
sox9 expression increases with malignant potential in tumors from patients with neurofibromatosis 1 and is not correlated to desert hedgehog.we investigated the expression of sox9, a transcription factor linked to the hedgehog pathways, and desert hedgehog, previously shown to be expressed in a malignant peripheral nerve sheath tumor cell line, in neurofibromatosis 1 tumors (neurofibromas and malignant peripheral nerve sheath tumor), and in a group of sporadic spindle cell sarcomas. we found that sox9 was expressed in schwann cells from neurofibromatosis 1 tumors, and was significantly up-regulated in malignant peripheral nerve sheat ...201021193222
identification of novel sry mutations and sf1 (nr5a1) changes in patients with pure gonadal dysgenesis and 46,xy karyotype.primary amenorrhea due to 46,xy disorders of sexual development (dsd) is complex with the involvement of several genes. karyotyping of such patients is important as they may develop dysgerminoma and molecular analysis is important to identify the underlying mechanism and explore the cascade of events occurring during sexual development. the present study was undertaken for the genetic analysis in seven patients from five families presenting with primary amenorrhea and diagnosed with pure gonadal ...201121242195
dual roles of the cardin-weintraub motif in multimeric sonic hedgehog.the fly morphogen hedgehog (hh) and its mammalian orthologs, sonic, indian and desert hedgehog are secreted signaling molecules that mediate tissue patterning during embryogenesis and function in tissue homeostasis and regeneration in the adult. the function of all hh family members is regulated at the levels of morphogen multimerization on the surface of producing cells, multimer release, multimer diffusion to target cells and signal reception. these mechanisms are all known to depend on intera ...201121572042
pharmacological inhibition of the hedgehog pathway prevents human rhabdomyosarcoma cell growth.the hedgehog pathway functions as an organizer in embryonic development. recent studies have shown that mutation of the ptch1 gene involved in the hedgehog pathway affects rhabdomyosarcoma development. however, the expression of hedgehog pathway molecules in human rhabdomyosarcoma cells has not been well clarified. in addition, the effect of pharmacological inhibition of the hedgehog pathway is not known. we investigated the expression of the genes involved in the hedgehog pathway using human rh ...201121674124
novel homozygous mutations in desert hedgehog gene in patients with 46,xy complete gonadal dysgenesis and prediction of its structural and functional implications by computational methods.male to female sex reversal in patients with 46,xy karyotype results from the failure of development of testis which may be due to mutations in the sry gene. only 10-15% of cases of 46,xy gonadal dysgenesis are accounted for by different types of mutations in the sry gene. hence, majority of such patients may have mutations in other genes involved in the testicular differentiation pathway. besides sry, other autosomal and x-linked genes are also involved in sexual development during embryogenesi ...201121816240
Desert hedgehog is a mammal-specific gene expressed during testicular and ovarian development in a marsupial.ABSTRACT: BACKGROUND: Desert hedgehog (DHH) belongs to the hedgehog gene family that act as secreted intercellular signal transducers. DHH is an essential morphogen for normal testicular development and function in both mice and humans but is not present in the avian lineage. Like other hedgehog proteins, DHH signals through the patched (PTCH) receptors 1 and 2. Here we examine the expression and protein distribution of DHH, PTCH1 and PTCH2 in the developing testes of a marsupial mammal (the ta ...201122132805
Hedgehog signalling promotes germ cell survival in the rat testis.Hedgehog (Hh) signalling has a crucial role in testis development. Sertoli cell-derived desert hedgehog (DHH) guides the formation of testis cords and differentiation of foetal-type Leydig cells. Dhh mutant mice are infertile due to a block in germ cell differentiation, hypogonadism and hypoandrogenism. Hh signalling pathway components are also expressed in postnatal testis. In the rat testis the transcription factor of the Hh pathway, glioma-associated oncogene homologue (GLI1), is expressed by ...201121893610
hedgehog signaling regulates myelination in the peripheral nervous system through primary cilia.myelination is an essential prerequisite for the nervous system to transmit an impulse efficiently by a saltatory conduction. in the peripheral nervous system (pns), schwann cells (scs) engage in myelination. however, a detailed molecular mechanism underlying myelination still remains unclear. in this study, we hypothesized that the primary cilia of scs are the regulators of hedgehog (hh) signaling-mediated myelination. to confirm our hypothesis, we used mouse dorsal root ganglion (drg)/sc co-cu ...201122101064
rickettsiae in arthropods collected from the north african hedgehog (atelerix algirus) and the desert hedgehog (paraechinus aethiopicus) in algeria.hedgehogs have become a popular pet despite their potential role in zoonotic disease transmission. we conducted an entomological study in a mountainous region of northeast algeria in which we collected 387 fleas (archeopsylla erinacei) and 342 ticks (rhipicephalus sanguineus and haemaphysalis erinacei) from paraechinus aethiopicus and atelerix algirus hedgehogs. of the hedgehogs sampled, 77.7% and 91% were infested with fleas and ticks, respectively. significantly more ticks and fleas were colle ...201222222114
conditional inactivation of pten with egfr overexpression in schwann cells models sporadic mpnst.the genetic mechanisms involved in the transformation from a benign neurofibroma to a malignant sarcoma in patients with neurofibromatosis-type-1- (nf1-)associated or sporadic malignant peripheral nerve sheath tumors (mpnsts) remain unclear. it is hypothesized that many genetic changes are involved in transformation. recently, it has been shown that both phosphatase and tensin homolog (pten) and epidermal growth factor receptor (egfr) play important roles in the initiation of peripheral nerve sh ...201223319880
mouse testis development and function are differently regulated by follicle-stimulating hormone receptors signaling during fetal and prepubertal life.it is currently admitted that follicle-stimulating hormone (fsh) is physiologically involved in the development and function of fetal/neonatal sertoli cells in the rat but not the mouse. however, fsh is produced by both species from late fetal life onwards. we thus reinvestigated the role of fsh in mouse testis development at day 0 (birth) 6, 8 and 10 post-partum (dpp) by using mice that lack functional fsh receptors (fsh-r(-/-)). at birth, the number and proliferative index of sertoli cells wer ...201223300903
mutation analysis of mitogen activated protein kinase 1 gene in indian cases of 46,xy disorder of sex development.determination of sex is the result of cascade of molecular events that cause undifferentiated bipotential gonad to develop as a testis or an ovary. a series of genes such as sry, steroidogenic factor-1 (sf1), ar, srd5 α, desert hedgehog (dhh) etc., have been reported to have a significant role in development of sex in the fetus and secondary sexual characteristics at the time of puberty. recently, mitogen activated protein kinase kinase kinase 1 (map3k1) gene was found to be associated with 46, ...024497709
first report of natural infection in hedgehogs with leishmania major, a possible reservoir of zoonotic cutaneous leishmaniasis in algeria.we report here the first known cases of natural infection of hedgehogs with leishmania major. cutaneous leishmaniasis is an important public health problem in the area of m'sila, a semi-arid province in algeria's northern sahara, where two species of hedgehog live, atelerix algirus and paraechinus aethiopicus. the aim of this research was to survey leishmania infection in these hedgehogs and evaluate whether they were reservoir hosts of leishmania in an endemic zoonotic focus of leishmaniasis. s ...201424699087
projections of nucleus caudalis and spinal cord to brainstem and diencephalon in the hedgehog (erinaceus europaeus and paraechinus aethiopicus): a degeneration study.in the light of hypotheses related to the evolution of pain-carrying systems in mammals, terminal projection fields in brainstem and diencephalon of efferents of nucleus caudalis (nc) of the spinal trigeminal complex and spinal cord were determined in hedgehog by using nauta-gygax and fink-heimer silver techniques for degeneration. unilateral nc lesions resulted in medullary degeneration in the ventral portion of nc contralaterally and bilaterally in cuneate nucleus (cu) and reticular formation. ...19836863599
[dura conditions, brain vessels and capillary density in the brains of the european hedgehog (erinaceus europaeus) and the desert hedgehog (erinaceus algirus levaudeni)]. 19685717246
morphological and molecular descriptions of moniliformis saudi sp. n. (acanthocephala: moniliformidae) from the desert hedgehog, paraechinus aethiopicus (ehrenberg) in saudi arabia, with a key to species and notes on histopathology.a new acanthocepohalan species, moniliformis saudi sp. n. is described from the desert hedgehog, paraechinus aethiopicus (ehrenberg), in central saudi arabia. fourteen other valid species of moniliformis travassos, 1915 are recognised. the new species of moniliformis is distinguished by having a small proboscis (315-520 µm long and 130-208 µm wide) with two apical pores, 14 rows of 8 hooks each and small hooks, thre largest being 25-31 µm long anteriorly. distinguishing features are incorporated ...201627189420
the comparative gastrointestinal morphology of jaculus jaculus (rodentia) and paraechinus aethiopicus (erinaceomorpha).jaculus jaculus (lesser egyptian jerboa) and paraechinus aethiopicus (desert hedgehog) are small mammals which thrive in desert conditions and are found, among others, in the arabian peninsula. jaculus jaculus is omnivorous while p. aethiopicus is described as being insectivorous. the study aims to describe the gastrointestinal tract (git) morphology of these animals which differ in diet and phylogeny. the gits of j. jaculus (n = 8) and p. aethiopicus (n = 7) were weighed, photographed, and the ...201626968578
shh/ptch and egf/erbb cooperatively regulate branching morphogenesis of fetal mouse submandibular glands.the hedgehog family includes sonic hedgehog (shh), desert hedgehog, and indian hedgehog, which are well known as a morphogens that play many important roles during development of numerous organs such as the tongue, pancreas, kidney, cartilage, teeth and salivary glands (smg). in shh null mice, abnormal development of the salivary gland is seen after embryonic day 14 (e14). shh also induced lobule formation and lumen formation in acini-like structures in cultured e14 smg. in this study, we invest ...201626930157
modulation of dhh signaling and altered sertoli cell function in mice lacking the gpr37-prosaposin receptor.the mammalian g-protein-coupled receptor 37 (gpr37) is expressed in brain, in adult testis, and during the early phase of gonad differentiation. somatic sertoli cells (scs) are located within the seminiferous tubules where they support the germinal epithelium. an adequate number of scs is required for the complete prepubertal differentiation of germ cells and adult fertility. this study shows that gpr37 and its ligand prosaposin are both postnatally expressed by scs, whose proliferation and matu ...201525609427
interaction between hedgehog signalling and pax6 dosage mediates maintenance and regeneration of the corneal epithelium.to investigate the roles of intracellular signaling elicited by hedgehog (hh) ligands in corneal maintenance and wound healing.201222275805
sertoli cell signaling by desert hedgehog regulates the male germline.in mammals, testis development is initiated in the embryo in response to the expression of the sex determining gene, sry, in sertoli cell precursors. subsequently, sertoli cells are thought to play a central role in male-specific cell interactions, including those that occur during spermatogenesis. however, the molecular nature of these interactions is poorly understood. desert hedgehog (dhh) encodes a signaling molecule expressed in the testis, but not the ovary, and may therefore play a role i ...19968805249
divergent axial morphogenesis and earlyshhexpression in vertebrate prospective floor plate.the notochord has organizer properties and is required for floor plate induction and dorsoventral patterning of the neural tube. this activity has been attributed to sonic hedgehog (shh) signaling, which originates in the notochord, forms a gradient, and autoinducesshhexpression in the floor plate. however, reported data are inconsistent and the spatiotemporal development of the relevantshhexpression domains has not been studied in detail. we therefore studied the expression dynamics ofshhin rab ...201829423139
hedgehog signaling in development and homeostasis of the gastrointestinal tract.the hedgehog family of secreted morphogenetic proteins acts through a complex evolutionary conserved signaling pathway to regulate patterning events during development and in the adult organism. in this review i discuss the role of hedgehog signaling in the development, postnatal maintenance, and carcinogenesis of the gastrointestinal tract. three mammalian hedgehog genes, sonic hedgehog (shh), indian hedgehog (ihh), and desert hedgehog (dhh) have been identified. shh and ihh are important endod ...200717928586
targeting the hedgehog pathway to mitigate treatment resistance.'hedgehog' (hh) molecules are secretory signaling proteins that were first discovered in drosophila. three hh homologs have been identified in humans including sonic hedgehog (shh), indian hedgehog (ihh) and desert hedgehog (dhh). during embryonic development, the hedgehog (hh) signaling pathway is critical, and it regulates both proliferation and differentiation of various types of stem cells.1this article provides a brief overview of hh signaling, summarizes the correlation between hh signalin ...200717671418
mutations in the desert hedgehog (dhh) gene in patients with 46,xy complete pure gonadal dysgenesis.mutations of sry are the cause of complete pure gonadal dysgenesis (pgd) in 10-15% of patients. in the remaining individuals, it has been suggested that mutations in other genes involved in the testis-determining pathway could be causative. we describe the first report in which three cases of 46,xy complete pgd are attributed to mutations of the desert hedgehog (dhh) gene. dhh was sequenced using genomic dna from paraffin-embedded gonadal tissue from six patients with complete 46,xy pgd. mutatio ...200415356051
nuclear organisation of some immunohistochemically identifiable neural systems in five species of insectivore-crocidura cyanea, crocidura olivieri, sylvisorex ollula, paraechinus aethiopicus and atelerix frontalis.the organization of the cholinergic, catecholaminergic, and serotonergic neurons in the brains of five species of insectivores and the orexinergic (hypocretinergic) system in four insectivore species is presented. we aimed to investigate the nuclear complement of these neural systems in comparison to those of other mammalian species. brains of insectivores were coronally sectioned and immunohistochemically stained with antibodies against choline acetyltransferase, tyrosine hydroxylase, serotonin ...201626724499
novel familial variant of the desert hedgehog gene: clinical findings in two sisters with 46,xy gonadal dysgenesis or 46,xx karyotype and literature review.in humans, desert hedgehog (dhh) gene mutations are a very rare cause of 46,xy gonadal dysgenesis (gd), eventually associated with peripheral neuropathy.201829471294
genetic screening of iranian patients with 46,xy disorders of sex development.disorders of sex development (dsds) belong to uncommon pathologies and result from abnormalities during gonadal determination and differentiation. various gene mutations involved in gonadal determination and differentiation have been associated with gonadal dysgenesis. despite advances in exploration of genes and mechanisms involved in sex disorders, most children with severe 46,xy dsds have no definitive etiological diagnoses; therefore, the possibility that other genes or loci might play impor ...201729090230
a brief exposure to cadmium impairs leydig cell regeneration in the adult rat testis.cadmium is an endocrine disruptor, impairing male reproduction. the objective of this study is to investigate whether cadmium affects rat leydig cell regeneration and to dissect the underlying mechanism. adult male sprague-dawley rats received a single intraperitoneal injection (i.p.) of 0, 0.5 or 1.0 mg/kg of cadmium chloride, followed by ethane dimethane sulfonate (eds) treatment to eliminate adult leydig cells 20 days later. compared to control (0 dose), cadmium treatment reduced serum testos ...201728740105
a novel variant of dhh in a familial case of 46,xy disorder of sex development: insights from molecular dynamics simulations.disorders of sex development (dsd) are a heterogeneous group of conditions affecting the differentiation and development of the internal and external genitalia. here, we aimed at identifying the genetic cause of dsd in two 46,xy sisters from a consanguineous family.201728708305
insights into the development of the adult leydig cell lineage from stem leydig cells.adult leydig cells (alcs) are the steroidogenic cells in the testes that produce testosterone. alcs develop postnatally from a pool of stem cells, referred to as stem leydig cells (slcs). slcs are spindle-shaped cells that lack steroidogenic cell markers, including luteinizing hormone (lh) receptor and 3β-hydroxysteroid dehydrogenase. the commitment of slcs into the progenitor leydig cells (plcs), the first stage in the lineage, requires growth factors, including dessert hedgehog (dhh) and plate ...201728701961
partial duplication ofdhhcauses minifascicular neuropathy: a novel mutation detection ofdhh.minifascicular neuropathy (mn) is an extremely rare developmental malformation in which peripheral nerves are composed of many small fascicles. only one patient with mn with 46xy gonadal dysgenesis (gd) was found to carry a mutation affecting the start codon indesert hedgehog(dhh). we identified an identical novel rearrangement mutation ofdhhin two consanguineous families with mn, confirming mutations indhhcause mn with 46xy gd. the patients with the 46xy karyotype developed gd, whereas a patien ...201728589169
torpor patterns in desert hedgehogs (paraechinus aethiopicus) represent another new point along a thermoregulatory continuum.documenting variation in thermoregulatory patterns across phylogenetically and geographically diverse taxa is key to understanding the evolution of endothermy and heterothermy in birds and mammals. we recorded body temperature (tb) in free-ranging desert hedgehogs (paraechinus aethiopicus) across three seasons in the deserts of saudi arabia. modal tb's (35°-36.5°c) were slightly below normal for mammals but still warmer than those of other hedgehogs. the single maximum tbrecorded was 39.2°c, whi ...201728402233
genetic evidence supporting the taxonomic separation of the arabian and northwest african subspecies of the desert hedgehog (paraechinus aethiopicus).traditional subspecies call attention to differences between geographic populations with research potential, but their value is often in need of revision. genetic data can be useful for evaluating the taxonomic validity of historical species and subspecies designations or for identifying morphologically cryptic divergent lineages worthy of further in-depth taxonomic study. the desert hedgehog (paraechinus aethiopicus) has a wide but fragmented distribution in arid and semi-arid habitats from the ...201728400268
vascular cell transcriptomic changes to exercise training differ directionally along and between skeletal muscle arteriolar trees.ext-induced arteriolar adaptations in skeletal muscle are heterogeneous because of spatial variations in muscle fiber type composition and fiber recruitment patterns during exercise. the purpose of this report is to summarize a series of experiments conducted to test the hypothesis that changes in vascular gene expression are signaled by alterations in shear stress resulting from increases in blood flow, muscle fiber type composition, and fiber recruitment patterns. we also report results from a ...201727889934
leydig cell stem cells: identification, proliferation and differentiation.adult leydig cells develop from undifferentiated mesenchymal-like stem cells (stem leydig cells, slcs) present in the interstitial compartment of the early postnatal testis. putative slcs also have been identified in peritubular and perivascular locations of the adult testis. the latter cells, which normally are quiescent, are capable of regenerating new leydig cells upon the loss of the adult cells. recent studies have identified several protein markers to identify these cells, including nestin ...201727743991
cell interactions and genetic regulation that contribute to testicular leydig cell development and differentiation.leydig cells, located within the interstitial compartment of the testis, are major contributors of androgen synthesis and secretion, which play an important role in testis development, normal masculinization, maintenance of spermatogenesis, and general male fertility. accordingly, dysfunction of leydig cells may lead to various male reproductive maladies, including primary hypogonadism, cryptorchidism, and hypospadias. a better understanding of how cell interactions and gene regulation contribut ...201627079813
regulation of seminiferous tubule-associated stem leydig cells in adult rat testes.testicular leydig cells are the primary source of testosterone in males. adult leydig cells have been shown to arise from stem cells present in the neonatal testis. once established, adult leydig cells turn over only slowly during adult life, but when these cells are eliminated experimentally from the adult testis, new leydig cells rapidly reappear. as in the neonatal testis, stem cells in the adult testis are presumed to be the source of the new leydig cells. as yet, the mechanisms involved in ...201626929346
impaired hedgehog signalling-induced endothelial dysfunction is sufficient to induce neuropathy: implication in diabetes.microangiopathy, i.e. endothelial dysfunction, has long been suggested to contribute to the development of diabetic neuropathy, although this has never been fully verified. in the present paper, we have identified the role of hedgehog (hh) signalling in endoneurial microvessel integrity and evaluated the impact of impaired hh signalling in endothelial cells (ecs) on nerve function.201626645982
desert hedgehog/patch2 axis contributes to vascular permeability and angiogenesis in glioblastoma.glioblastoma multiforme (gbm) constitutes the most common and the most aggressive type of human tumors affecting the central nervous system. prognosis remains dark due to the inefficiency of current treatments and the rapid relapse. paralleling other human tumors, gbm contains a fraction of tumor initiating cells with the capacity to self-renew, initiate and maintain the tumor mass. these cells were found in close proximity to brain vasculature, suggesting functional interactions between brain t ...201526635611
hedgehog- and mtor-targeted therapies for advanced basal cell carcinomas.basal cell carcinomas (bccs) are the most frequent human cancer. over 90% of all bccs have a mutation in ptch1 or smoothened, two conducting proteins of the hedgehog pathway. they rarely progress deeply and metastasize; however, if they do, these advanced basal cell carcinoma become amenable to treatment by inhibiting the hedgehog and the p13k-mtor pathways. such innovative drugs include vismodegib, cyclopamine, itraconazole, everolimus and a few other agents that are in early clinical developme ...201526437034
hedgehog signaling in malignant pleural mesothelioma.malignant pleural mesothelioma (mpm) is a cancer associated with exposure to asbestos fibers, which accumulate in the pleural space, damage tissue and stimulate regeneration. hedgehog signaling is a pathway important during embryonic mesothelium development and is inactivated in adult mesothelium. the pathway is reactivated in some mpm patients with poor clinical outcome, mainly mediated by the expression of the ligands. nevertheless, mutations in components of the pathway have been observed in ...201526184317
exercise-induced differential changes in gene expression among arterioles of skeletal muscles of obese rats.using next-generation, transcriptome-wide rna sequencing (rna-seq) technology we assessed the effects of exercise training on transcriptional profiles in skeletal muscle arterioles isolated from the soleus and gastrocnemius muscles of otsuka long evans tokushima fatty (oletf) rats that underwent an endurance exercise training program (ex; n = 13), interval sprint training program (sprint; n = 14), or remained sedentary (sed; n = 12). we hypothesized that the greatest effects of exercise would be ...201526183477
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