The Experts below are selected from a list of 105 Experts worldwide ranked by ideXlab platform
Jorge Filmus - One of the best experts on this subject based on the ideXlab platform.
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overgrowth of a mouse model of simpson golabi behmel syndrome is partly mediated by indian hedgehog
EMBO Reports, 2009Co-Authors: Mariana I Capurro, Jorge FilmusAbstract:Loss-of-function mutations of Glypican 3 (Gpc3) cause the Simpson–Golabi–Behmel overgrowth syndrome (SGBS), and developmental overgrowth is observed in Gpc3-null mice, a mouse model for SGBS. We recently reported that GPC3 inhibits Hedgehog (Hh) signalling by inducing its endocytosis and degradation. Here, we show that the developmental overgrowth observed in Gpc3-null mice is, at least in part, a consequence of the hyperactivation of the Hh pathway. We bred Gpc3-null mice with mice that are Hh signalling-deficient owing to the lack of Indian Hh (IHH), one of the three mammalian Hhs. We found that the Gpc3-null mice showed a 29.9% overgrowth in an IHH wild-type background, whereas an IHH-null background partly rescues the overgrowth caused by the lack of Gpc3 as the double mutants were 19.8% bigger than the IHH-null mice. Consistent with the role of GPC3 in Hh endocytosis and degradation, the Gpc3-null mice show increased levels of IHH Protein and signalling, but similar levels of IHH messenger RNA.
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Overgrowth of a mouse model of Simpson– Golabi–Behmel syndrome is partly mediated by Indian Hedgehog
EMBO reports, 2009Co-Authors: Mariana I Capurro, Jorge FilmusAbstract:Loss-of-function mutations of Glypican 3 (Gpc3) cause the Simpson–Golabi–Behmel overgrowth syndrome (SGBS), and developmental overgrowth is observed in Gpc3-null mice, a mouse model for SGBS. We recently reported that GPC3 inhibits Hedgehog (Hh) signalling by inducing its endocytosis and degradation. Here, we show that the developmental overgrowth observed in Gpc3-null mice is, at least in part, a consequence of the hyperactivation of the Hh pathway. We bred Gpc3-null mice with mice that are Hh signalling-deficient owing to the lack of Indian Hh (IHH), one of the three mammalian Hhs. We found that the Gpc3-null mice showed a 29.9% overgrowth in an IHH wild-type background, whereas an IHH-null background partly rescues the overgrowth caused by the lack of Gpc3 as the double mutants were 19.8% bigger than the IHH-null mice. Consistent with the role of GPC3 in Hh endocytosis and degradation, the Gpc3-null mice show increased levels of IHH Protein and signalling, but similar levels of IHH messenger RNA.
Mariana I Capurro - One of the best experts on this subject based on the ideXlab platform.
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overgrowth of a mouse model of simpson golabi behmel syndrome is partly mediated by indian hedgehog
EMBO Reports, 2009Co-Authors: Mariana I Capurro, Jorge FilmusAbstract:Loss-of-function mutations of Glypican 3 (Gpc3) cause the Simpson–Golabi–Behmel overgrowth syndrome (SGBS), and developmental overgrowth is observed in Gpc3-null mice, a mouse model for SGBS. We recently reported that GPC3 inhibits Hedgehog (Hh) signalling by inducing its endocytosis and degradation. Here, we show that the developmental overgrowth observed in Gpc3-null mice is, at least in part, a consequence of the hyperactivation of the Hh pathway. We bred Gpc3-null mice with mice that are Hh signalling-deficient owing to the lack of Indian Hh (IHH), one of the three mammalian Hhs. We found that the Gpc3-null mice showed a 29.9% overgrowth in an IHH wild-type background, whereas an IHH-null background partly rescues the overgrowth caused by the lack of Gpc3 as the double mutants were 19.8% bigger than the IHH-null mice. Consistent with the role of GPC3 in Hh endocytosis and degradation, the Gpc3-null mice show increased levels of IHH Protein and signalling, but similar levels of IHH messenger RNA.
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Overgrowth of a mouse model of Simpson– Golabi–Behmel syndrome is partly mediated by Indian Hedgehog
EMBO reports, 2009Co-Authors: Mariana I Capurro, Jorge FilmusAbstract:Loss-of-function mutations of Glypican 3 (Gpc3) cause the Simpson–Golabi–Behmel overgrowth syndrome (SGBS), and developmental overgrowth is observed in Gpc3-null mice, a mouse model for SGBS. We recently reported that GPC3 inhibits Hedgehog (Hh) signalling by inducing its endocytosis and degradation. Here, we show that the developmental overgrowth observed in Gpc3-null mice is, at least in part, a consequence of the hyperactivation of the Hh pathway. We bred Gpc3-null mice with mice that are Hh signalling-deficient owing to the lack of Indian Hh (IHH), one of the three mammalian Hhs. We found that the Gpc3-null mice showed a 29.9% overgrowth in an IHH wild-type background, whereas an IHH-null background partly rescues the overgrowth caused by the lack of Gpc3 as the double mutants were 19.8% bigger than the IHH-null mice. Consistent with the role of GPC3 in Hh endocytosis and degradation, the Gpc3-null mice show increased levels of IHH Protein and signalling, but similar levels of IHH messenger RNA.
Nancy B Schwartz - One of the best experts on this subject based on the ideXlab platform.
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sulfation of chondroitin sulfate proteoglycans is necessary for proper indian hedgehog signaling in the developing growth plate
Development, 2009Co-Authors: Mauricio Cortes, Alexis T Baria, Nancy B SchwartzAbstract:In contrast to the functional role of heparan sulfate proteoglycans (HSPGs), the importance of chondroitin sulfate proteoglycans (CSPGs) in modulating signaling pathways involving hedgehog Proteins, wingless-related Proteins and fibroblast growth factors remains unclear. To elucidate the importance of sulfated CSPGs in signaling paradigms required for endochondral bone formation, the brachymorphic (bm) mouse was used as a model for undersulfated CSPGs. The bm mouse exhibits a postnatal chondrodysplasia caused by a mutation in the phosphoadenosine phosphosulfate (PAPS) synthetase (Papss2) gene, leading to reduced levels of PAPS and undersulfated proteoglycans. Biochemical analysis of the glycosaminoglycan (GAG) content in bm cartilage via sulfate labeling and fluorophore-assisted carbohydrate electrophoresis revealed preferential undersulfation of chondroitin chains (CS) and normal sulfation of heparan sulfate chains. In situ hybridization and immunohistochemical analysis of bm limb growth plates showed diminished Indian hedgehog (IHH) signaling and abnormal IHH Protein distribution in the extracellular matrix. Consistent with the decrease in hedgehog signaling, BrdU incorporation exhibited a significant reduction in chondrocyte proliferation. Direct measurements of IHH binding to defined GAG chains demonstrated that IHH interacts with CS, particularly chondroitin-4-sulfate. Furthermore, co-immunoprecipitation experiments showed that IHH binds to the major cartilage CSPG aggrecan via its CS chains. Overall, this study demonstrates an important function for CSPGs in modulating IHH signaling in the developing growth plate, and highlights the importance of carbohydrate sulfation in regulating growth factor signaling.
E De Graaff - One of the best experts on this subject based on the ideXlab platform.
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Deletion of 1 amino acid in Indian hedgehog leads to brachydactylyA1.
American journal of medical genetics. Part A, 2008Co-Authors: E M Lodder, A J M Hoogeboom, J H Coert, E De GraaffAbstract:Brachydactyly type A1 is a limb malformation characterized by a uniform shortening of the middle phalanges in all digits. Mutations in the Indian hedgehog (IHH) gene were shown to be the cause of this autosomal dominant disorder. The IHH Protein is known to be an important signaling molecule involved in chondrocyte formation. So far, only missense mutations in IHH have been reported to cause BrachydactylyA1. We report here on the first deletion in IHH, p.delE95, causing mild BrachydactylyA1 in a small Dutch family. This brings the total number of different mutations found to cause BDA1 to 7.
Bing Wang - One of the best experts on this subject based on the ideXlab platform.
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Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway.
Aging, 2020Co-Authors: Mahmoud Al-azab, Bing Wang, Abdalkhalig Elkhider, Williams Walana, Bo Yuan, Yawei Tang, Marwan Almoiliqy, Salah AdlatAbstract:Premature senescence of bone marrow-derived mesenchymal stem cells (BMSC) remains a major concern for their application clinically. Hedgehog signaling has been reported to regulate aging-associated markers and MSC skewed differentiation. Indian Hedgehog (IHH) is a ligand of Hedgehog intracellular pathway considered as an inducer in chondrogenesis of human BMSC. However, the role of IHH in the aging of BMSC is still unclear. This study explored the role IHH in the senescence of BMSC obtained from human samples and senescent mice. Isolated BMSC were transfected with IHH siRNA or incubated with exogenous IHH Protein and the mechanisms of aging and differentiation investigated. Moreover, the interactions between IHH, and mammalian target of rapamycin (mTOR) and reactive oxygen species (ROS) were evaluated using the corresponding inhibitors and antioxidants. BMSC transfected with IHH siRNA showed characteristics of senescence-associated features including increased senescence-associated β-galactosidase activity (SA-β-gal), induction of cell cycle inhibitors (p53/p16), development of senescence-associated secretory phenotype (SASP), activation of ROS and mTOR pathways as well as the promotion of skewed differentiation. Interestingly, BMSC treatment with IHH Protein reversed the senescence markers and corrected biased differentiation. Moreover, IHH shortage-induced senescence signs were compromised after mTOR and ROS inhibition. Our findings presented anti-aging activity for IHH in BMSC through down-regulation of ROS/mTOR pathways. This discovery might contribute to increasing the therapeutic, immunomodulatory and regenerative potency of BMSC and introduce a novel remedy in the management of aging-related diseases.
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TL1A mediates fibroblast-like synoviocytes migration and Indian Hedgehog signaling pathway via TNFR2 in patients with rheumatoid arthritis.
European cytokine network, 2018Co-Authors: Mahmoud Al-azab, Abdalkhalig Elkhider, Williams Walana, Yawei Tang, Jing Wei, Xunli Ouyang, Xiaotong Sun, Bing WangAbstract:Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joints inflammation. One of the aggressive characteristics of RA fibroblast-like synoviocytes (FLS) is the tendency for migration in the local environment, which plays a central role in the RA pathogenesis. Tumor Necrosis Factor (TNF)-like cytokine 1A (TL1A) is a member of TNF superfamily, which has a role in autoimmunity and influences the RA-FLS behavior through TNF receptor 2 (TNFR2).We investigated the effect of TNF-like cytokine 1A (TL1A) on RA-FLS migration using patients’ samples. Specifically, we examined the hedgehog signaling pathway which is a key regulator in chondrocyte growth and differentiation. We found that TL1A increased significantly the hedgehog homologue Indian hedgehog (IHH) and its receptor Patched 1, 2 (PTCH 1, 2) in RA-FLS. In addition, TL1A-stimulated RA-FLS promoted significantly IHH Protein expression. However, both mRNA and Protein levels decreased substantially after blocking TL1A with TNFR2 antagonist. The migratory property of RA-FLS was enhanced after stimulation of RA-FLS with TL1A, but was compromised following TL1A blockage. In conclusion, our study has revealed that TL1A modulated RA-FLS migration and Indian hedgehog signaling pathway using TNFR2.
