The Experts below are selected from a list of 6612 Experts worldwide ranked by ideXlab platform
Xinyue Qin - One of the best experts on this subject based on the ideXlab platform.
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rgma mediates reactive astrogliosis and Glial Scar formation through tgfβ1 smad2 3 signaling after stroke
Cell Death & Differentiation, 2018Co-Authors: Rongrong Zhang, Fei Xie, Yiliang Zhong, Yu Wang, Jinzhou Feng, Jason Charish, Philippe P Monnier, Xinyue QinAbstract:In response to stroke, astrocytes become reactive astrogliosis and are a major component of a Glial Scar. This results in the formation of both a physical and chemical (production of chondroitin sulfate proteoglycans) barrier, which prevent neurite regeneration that, in turn, interferes with functional recovery. However, the mechanisms of reactive astrogliosis and Glial Scar formation are poorly understood. In this work, we hypothesized that repulsive guidance molecule a (RGMa) regulate reactive astrogliosis and Glial Scar formation. We first found that RGMa was strongly expressed by reactive astrocytes in the Glial Scar in a rat model of middle cerebral artery occlusion/reperfusion. Genetic or pharmacologic inhibition of RGMa in vivo resulted in a strong reduction of reactive astrogliosis and Glial Scarring as well as in a pronounced improvement in functional recovery. Furthermore, we showed that transforming growth factor β1 (TGFβ1) stimulated RGMa expression through TGFβ1 receptor activin-like kinase 5 (ALK5) in primary cultured astrocytes. Knockdown of RGMa abrogated key steps of reactive astrogliosis and Glial Scar formation induced by TGFβ1, including cellular hypertrophy, Glial fibrillary acidic protein upregulation, cell migration, and CSPGs secretion. Finally, we demonstrated that RGMa co-immunoprecipitated with ALK5 and Smad2/3. TGFβ1-induced ALK5-Smad2/3 interaction and subsequent phosphorylation of Smad2/3 were impaired by RGMa knockdown. Taken together, we identified that after stroke, RGMa promotes reactive astrogliosis and Glial Scar formation by forming a complex with ALK5 and Smad2/3 to promote ALK5-Smad2/3 interaction to facilitate TGFβ1/Smad2/3 signaling, thereby inhibiting neurological functional recovery. RGMa may be a new therapeutic target for stroke.
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RGMa mediates reactive astrogliosis and Glial Scar formation through TGFβ1/Smad2/3 signaling after stroke
Cell death and differentiation, 2018Co-Authors: Rongrong Zhang, Fei Xie, Yiliang Zhong, Yu Wang, Jinzhou Feng, Jason Charish, Philippe P Monnier, Xinyue QinAbstract:In response to stroke, astrocytes become reactive astrogliosis and are a major component of a Glial Scar. This results in the formation of both a physical and chemical (production of chondroitin sulfate proteoglycans) barrier, which prevent neurite regeneration that, in turn, interferes with functional recovery. However, the mechanisms of reactive astrogliosis and Glial Scar formation are poorly understood. In this work, we hypothesized that repulsive guidance molecule a (RGMa) regulate reactive astrogliosis and Glial Scar formation. We first found that RGMa was strongly expressed by reactive astrocytes in the Glial Scar in a rat model of middle cerebral artery occlusion/reperfusion. Genetic or pharmacologic inhibition of RGMa in vivo resulted in a strong reduction of reactive astrogliosis and Glial Scarring as well as in a pronounced improvement in functional recovery. Furthermore, we showed that transforming growth factor β1 (TGFβ1) stimulated RGMa expression through TGFβ1 receptor activin-like kinase 5 (ALK5) in primary cultured astrocytes. Knockdown of RGMa abrogated key steps of reactive astrogliosis and Glial Scar formation induced by TGFβ1, including cellular hypertrophy, Glial fibrillary acidic protein upregulation, cell migration, and CSPGs secretion. Finally, we demonstrated that RGMa co-immunoprecipitated with ALK5 and Smad2/3. TGFβ1-induced ALK5-Smad2/3 interaction and subsequent phosphorylation of Smad2/3 were impaired by RGMa knockdown. Taken together, we identified that after stroke, RGMa promotes reactive astrogliosis and Glial Scar formation by forming a complex with ALK5 and Smad2/3 to promote ALK5-Smad2/3 interaction to facilitate TGFβ1/Smad2/3 signaling, thereby inhibiting neurological functional recovery. RGMa may be a new therapeutic target for stroke.
Isabelle Dusart - One of the best experts on this subject based on the ideXlab platform.
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long term changes in the molecular composition of the Glial Scar and progressive increase of serotoninergic fibre sprouting after hemisection of the mouse spinal cord
European Journal of Neuroscience, 2004Co-Authors: Emeline Camand, Mariepierre Morel, Andreas Faissner, Constantino Sotelo, Isabelle DusartAbstract:The Scarring process occurring after adult central nervous system injury and the subsequent increase in the expression of certain extracellular matrix molecules are known to contribute to the failure of axon regeneration. This study provides an immunohistochemical analysis of temporal changes (8 days to 1 year) in the cellular and molecular response of the Swiss mouse spinal cord to a dorsal hemisection and its correlation with the axonal growth properties of a descending pathway, the serotoninergic axons. In this lesion model, no cavity forms at the centre of the lesion. Instead, a dense fibronectin-positive tissue matrix occupies the centre of the lesion, surrounded by a Glial Scar mainly constituted by reactive astrocytes. NG2 proteoglycan and tenascin-C, potential axon growth inhibitors, are constantly associated with the central region. In the Glial Scar, tenascin-C is never observed and the expression of chondroitin sulphate proteoglycans (revealed with CS-56 and anti-NG2 antibodies) highly increases in the week following injury to progressively return to their control level. In parallel, there is an increasing expression of the polysialilated neural cell adhesion molecule by reactive astrocytes. These molecular changes are correlated with a sprouting process of serotoninergic axons in the Glial Scar, except in a small area in contact with the central region. All these observations suggest that while a part of the Glial Scar progressively becomes permissive to axon regeneration after mouse spinal cord injury, the border of the Glial Scar, in contact with the fibronectin-positive tissue matrix, is the real barrier to prevent axon regeneration.
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Long‐term changes in the molecular composition of the Glial Scar and progressive increase of serotoninergic fibre sprouting after hemisection of the mouse spinal cord
The European journal of neuroscience, 2004Co-Authors: Emeline Camand, Mariepierre Morel, Andreas Faissner, Constantino Sotelo, Isabelle DusartAbstract:The Scarring process occurring after adult central nervous system injury and the subsequent increase in the expression of certain extracellular matrix molecules are known to contribute to the failure of axon regeneration. This study provides an immunohistochemical analysis of temporal changes (8 days to 1 year) in the cellular and molecular response of the Swiss mouse spinal cord to a dorsal hemisection and its correlation with the axonal growth properties of a descending pathway, the serotoninergic axons. In this lesion model, no cavity forms at the centre of the lesion. Instead, a dense fibronectin-positive tissue matrix occupies the centre of the lesion, surrounded by a Glial Scar mainly constituted by reactive astrocytes. NG2 proteoglycan and tenascin-C, potential axon growth inhibitors, are constantly associated with the central region. In the Glial Scar, tenascin-C is never observed and the expression of chondroitin sulphate proteoglycans (revealed with CS-56 and anti-NG2 antibodies) highly increases in the week following injury to progressively return to their control level. In parallel, there is an increasing expression of the polysialilated neural cell adhesion molecule by reactive astrocytes. These molecular changes are correlated with a sprouting process of serotoninergic axons in the Glial Scar, except in a small area in contact with the central region. All these observations suggest that while a part of the Glial Scar progressively becomes permissive to axon regeneration after mouse spinal cord injury, the border of the Glial Scar, in contact with the fibronectin-positive tissue matrix, is the real barrier to prevent axon regeneration.
Philippe P Monnier - One of the best experts on this subject based on the ideXlab platform.
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rgma mediates reactive astrogliosis and Glial Scar formation through tgfβ1 smad2 3 signaling after stroke
Cell Death & Differentiation, 2018Co-Authors: Rongrong Zhang, Fei Xie, Yiliang Zhong, Yu Wang, Jinzhou Feng, Jason Charish, Philippe P Monnier, Xinyue QinAbstract:In response to stroke, astrocytes become reactive astrogliosis and are a major component of a Glial Scar. This results in the formation of both a physical and chemical (production of chondroitin sulfate proteoglycans) barrier, which prevent neurite regeneration that, in turn, interferes with functional recovery. However, the mechanisms of reactive astrogliosis and Glial Scar formation are poorly understood. In this work, we hypothesized that repulsive guidance molecule a (RGMa) regulate reactive astrogliosis and Glial Scar formation. We first found that RGMa was strongly expressed by reactive astrocytes in the Glial Scar in a rat model of middle cerebral artery occlusion/reperfusion. Genetic or pharmacologic inhibition of RGMa in vivo resulted in a strong reduction of reactive astrogliosis and Glial Scarring as well as in a pronounced improvement in functional recovery. Furthermore, we showed that transforming growth factor β1 (TGFβ1) stimulated RGMa expression through TGFβ1 receptor activin-like kinase 5 (ALK5) in primary cultured astrocytes. Knockdown of RGMa abrogated key steps of reactive astrogliosis and Glial Scar formation induced by TGFβ1, including cellular hypertrophy, Glial fibrillary acidic protein upregulation, cell migration, and CSPGs secretion. Finally, we demonstrated that RGMa co-immunoprecipitated with ALK5 and Smad2/3. TGFβ1-induced ALK5-Smad2/3 interaction and subsequent phosphorylation of Smad2/3 were impaired by RGMa knockdown. Taken together, we identified that after stroke, RGMa promotes reactive astrogliosis and Glial Scar formation by forming a complex with ALK5 and Smad2/3 to promote ALK5-Smad2/3 interaction to facilitate TGFβ1/Smad2/3 signaling, thereby inhibiting neurological functional recovery. RGMa may be a new therapeutic target for stroke.
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RGMa mediates reactive astrogliosis and Glial Scar formation through TGFβ1/Smad2/3 signaling after stroke
Cell death and differentiation, 2018Co-Authors: Rongrong Zhang, Fei Xie, Yiliang Zhong, Yu Wang, Jinzhou Feng, Jason Charish, Philippe P Monnier, Xinyue QinAbstract:In response to stroke, astrocytes become reactive astrogliosis and are a major component of a Glial Scar. This results in the formation of both a physical and chemical (production of chondroitin sulfate proteoglycans) barrier, which prevent neurite regeneration that, in turn, interferes with functional recovery. However, the mechanisms of reactive astrogliosis and Glial Scar formation are poorly understood. In this work, we hypothesized that repulsive guidance molecule a (RGMa) regulate reactive astrogliosis and Glial Scar formation. We first found that RGMa was strongly expressed by reactive astrocytes in the Glial Scar in a rat model of middle cerebral artery occlusion/reperfusion. Genetic or pharmacologic inhibition of RGMa in vivo resulted in a strong reduction of reactive astrogliosis and Glial Scarring as well as in a pronounced improvement in functional recovery. Furthermore, we showed that transforming growth factor β1 (TGFβ1) stimulated RGMa expression through TGFβ1 receptor activin-like kinase 5 (ALK5) in primary cultured astrocytes. Knockdown of RGMa abrogated key steps of reactive astrogliosis and Glial Scar formation induced by TGFβ1, including cellular hypertrophy, Glial fibrillary acidic protein upregulation, cell migration, and CSPGs secretion. Finally, we demonstrated that RGMa co-immunoprecipitated with ALK5 and Smad2/3. TGFβ1-induced ALK5-Smad2/3 interaction and subsequent phosphorylation of Smad2/3 were impaired by RGMa knockdown. Taken together, we identified that after stroke, RGMa promotes reactive astrogliosis and Glial Scar formation by forming a complex with ALK5 and Smad2/3 to promote ALK5-Smad2/3 interaction to facilitate TGFβ1/Smad2/3 signaling, thereby inhibiting neurological functional recovery. RGMa may be a new therapeutic target for stroke.
Jason Charish - One of the best experts on this subject based on the ideXlab platform.
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rgma mediates reactive astrogliosis and Glial Scar formation through tgfβ1 smad2 3 signaling after stroke
Cell Death & Differentiation, 2018Co-Authors: Rongrong Zhang, Fei Xie, Yiliang Zhong, Yu Wang, Jinzhou Feng, Jason Charish, Philippe P Monnier, Xinyue QinAbstract:In response to stroke, astrocytes become reactive astrogliosis and are a major component of a Glial Scar. This results in the formation of both a physical and chemical (production of chondroitin sulfate proteoglycans) barrier, which prevent neurite regeneration that, in turn, interferes with functional recovery. However, the mechanisms of reactive astrogliosis and Glial Scar formation are poorly understood. In this work, we hypothesized that repulsive guidance molecule a (RGMa) regulate reactive astrogliosis and Glial Scar formation. We first found that RGMa was strongly expressed by reactive astrocytes in the Glial Scar in a rat model of middle cerebral artery occlusion/reperfusion. Genetic or pharmacologic inhibition of RGMa in vivo resulted in a strong reduction of reactive astrogliosis and Glial Scarring as well as in a pronounced improvement in functional recovery. Furthermore, we showed that transforming growth factor β1 (TGFβ1) stimulated RGMa expression through TGFβ1 receptor activin-like kinase 5 (ALK5) in primary cultured astrocytes. Knockdown of RGMa abrogated key steps of reactive astrogliosis and Glial Scar formation induced by TGFβ1, including cellular hypertrophy, Glial fibrillary acidic protein upregulation, cell migration, and CSPGs secretion. Finally, we demonstrated that RGMa co-immunoprecipitated with ALK5 and Smad2/3. TGFβ1-induced ALK5-Smad2/3 interaction and subsequent phosphorylation of Smad2/3 were impaired by RGMa knockdown. Taken together, we identified that after stroke, RGMa promotes reactive astrogliosis and Glial Scar formation by forming a complex with ALK5 and Smad2/3 to promote ALK5-Smad2/3 interaction to facilitate TGFβ1/Smad2/3 signaling, thereby inhibiting neurological functional recovery. RGMa may be a new therapeutic target for stroke.
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RGMa mediates reactive astrogliosis and Glial Scar formation through TGFβ1/Smad2/3 signaling after stroke
Cell death and differentiation, 2018Co-Authors: Rongrong Zhang, Fei Xie, Yiliang Zhong, Yu Wang, Jinzhou Feng, Jason Charish, Philippe P Monnier, Xinyue QinAbstract:In response to stroke, astrocytes become reactive astrogliosis and are a major component of a Glial Scar. This results in the formation of both a physical and chemical (production of chondroitin sulfate proteoglycans) barrier, which prevent neurite regeneration that, in turn, interferes with functional recovery. However, the mechanisms of reactive astrogliosis and Glial Scar formation are poorly understood. In this work, we hypothesized that repulsive guidance molecule a (RGMa) regulate reactive astrogliosis and Glial Scar formation. We first found that RGMa was strongly expressed by reactive astrocytes in the Glial Scar in a rat model of middle cerebral artery occlusion/reperfusion. Genetic or pharmacologic inhibition of RGMa in vivo resulted in a strong reduction of reactive astrogliosis and Glial Scarring as well as in a pronounced improvement in functional recovery. Furthermore, we showed that transforming growth factor β1 (TGFβ1) stimulated RGMa expression through TGFβ1 receptor activin-like kinase 5 (ALK5) in primary cultured astrocytes. Knockdown of RGMa abrogated key steps of reactive astrogliosis and Glial Scar formation induced by TGFβ1, including cellular hypertrophy, Glial fibrillary acidic protein upregulation, cell migration, and CSPGs secretion. Finally, we demonstrated that RGMa co-immunoprecipitated with ALK5 and Smad2/3. TGFβ1-induced ALK5-Smad2/3 interaction and subsequent phosphorylation of Smad2/3 were impaired by RGMa knockdown. Taken together, we identified that after stroke, RGMa promotes reactive astrogliosis and Glial Scar formation by forming a complex with ALK5 and Smad2/3 to promote ALK5-Smad2/3 interaction to facilitate TGFβ1/Smad2/3 signaling, thereby inhibiting neurological functional recovery. RGMa may be a new therapeutic target for stroke.
Rongrong Zhang - One of the best experts on this subject based on the ideXlab platform.
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rgma mediates reactive astrogliosis and Glial Scar formation through tgfβ1 smad2 3 signaling after stroke
Cell Death & Differentiation, 2018Co-Authors: Rongrong Zhang, Fei Xie, Yiliang Zhong, Yu Wang, Jinzhou Feng, Jason Charish, Philippe P Monnier, Xinyue QinAbstract:In response to stroke, astrocytes become reactive astrogliosis and are a major component of a Glial Scar. This results in the formation of both a physical and chemical (production of chondroitin sulfate proteoglycans) barrier, which prevent neurite regeneration that, in turn, interferes with functional recovery. However, the mechanisms of reactive astrogliosis and Glial Scar formation are poorly understood. In this work, we hypothesized that repulsive guidance molecule a (RGMa) regulate reactive astrogliosis and Glial Scar formation. We first found that RGMa was strongly expressed by reactive astrocytes in the Glial Scar in a rat model of middle cerebral artery occlusion/reperfusion. Genetic or pharmacologic inhibition of RGMa in vivo resulted in a strong reduction of reactive astrogliosis and Glial Scarring as well as in a pronounced improvement in functional recovery. Furthermore, we showed that transforming growth factor β1 (TGFβ1) stimulated RGMa expression through TGFβ1 receptor activin-like kinase 5 (ALK5) in primary cultured astrocytes. Knockdown of RGMa abrogated key steps of reactive astrogliosis and Glial Scar formation induced by TGFβ1, including cellular hypertrophy, Glial fibrillary acidic protein upregulation, cell migration, and CSPGs secretion. Finally, we demonstrated that RGMa co-immunoprecipitated with ALK5 and Smad2/3. TGFβ1-induced ALK5-Smad2/3 interaction and subsequent phosphorylation of Smad2/3 were impaired by RGMa knockdown. Taken together, we identified that after stroke, RGMa promotes reactive astrogliosis and Glial Scar formation by forming a complex with ALK5 and Smad2/3 to promote ALK5-Smad2/3 interaction to facilitate TGFβ1/Smad2/3 signaling, thereby inhibiting neurological functional recovery. RGMa may be a new therapeutic target for stroke.
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RGMa mediates reactive astrogliosis and Glial Scar formation through TGFβ1/Smad2/3 signaling after stroke
Cell death and differentiation, 2018Co-Authors: Rongrong Zhang, Fei Xie, Yiliang Zhong, Yu Wang, Jinzhou Feng, Jason Charish, Philippe P Monnier, Xinyue QinAbstract:In response to stroke, astrocytes become reactive astrogliosis and are a major component of a Glial Scar. This results in the formation of both a physical and chemical (production of chondroitin sulfate proteoglycans) barrier, which prevent neurite regeneration that, in turn, interferes with functional recovery. However, the mechanisms of reactive astrogliosis and Glial Scar formation are poorly understood. In this work, we hypothesized that repulsive guidance molecule a (RGMa) regulate reactive astrogliosis and Glial Scar formation. We first found that RGMa was strongly expressed by reactive astrocytes in the Glial Scar in a rat model of middle cerebral artery occlusion/reperfusion. Genetic or pharmacologic inhibition of RGMa in vivo resulted in a strong reduction of reactive astrogliosis and Glial Scarring as well as in a pronounced improvement in functional recovery. Furthermore, we showed that transforming growth factor β1 (TGFβ1) stimulated RGMa expression through TGFβ1 receptor activin-like kinase 5 (ALK5) in primary cultured astrocytes. Knockdown of RGMa abrogated key steps of reactive astrogliosis and Glial Scar formation induced by TGFβ1, including cellular hypertrophy, Glial fibrillary acidic protein upregulation, cell migration, and CSPGs secretion. Finally, we demonstrated that RGMa co-immunoprecipitated with ALK5 and Smad2/3. TGFβ1-induced ALK5-Smad2/3 interaction and subsequent phosphorylation of Smad2/3 were impaired by RGMa knockdown. Taken together, we identified that after stroke, RGMa promotes reactive astrogliosis and Glial Scar formation by forming a complex with ALK5 and Smad2/3 to promote ALK5-Smad2/3 interaction to facilitate TGFβ1/Smad2/3 signaling, thereby inhibiting neurological functional recovery. RGMa may be a new therapeutic target for stroke.