The Experts below are selected from a list of 25623 Experts worldwide ranked by ideXlab platform
Penghui Wang - One of the best experts on this subject based on the ideXlab platform.
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nonsteroidal anti inflammatory drugs for wounds pain relief or excessive Scar Formation
Mediators of Inflammation, 2010Co-Authors: Minghuei Cheng, Wenling Lee, Tsung Shan Tsou, Wenhsun Chang, Chien Sheng Chen, Penghui WangAbstract:The inflammatory process has direct effects on normal and abnormal wound healing. Hypertrophic Scar Formation is an aberrant form of wound healing and is an indication of an exaggerated function of fibroblasts and excess accumulation of extracellular matrix during wound healing. Two cytokines--transforming growth factor-beta (TGF-beta) and prostaglandin E2 (PGE2)--are lipid mediators of inflammation involving wound healing. Overproduction of TGF-beta and suppression of PGE2 are found in excessive wound Scarring compared with normal wound healing. Nonsteroidal anti-inflammatory drugs (NSAIDs) or their selective cyclooxygenase-2 (COX-2) inhibitors are frequently used as a pain-killer. However, both NSAIDs and COX-2 inhibitors inhibit PGE2 production, which might exacerbate excessive Scar Formation, especially when used during the later proliferative phase. Therefore, a balance between cytokines and medication in the pathogenesis of wound healing is needed. This report is a literature review pertaining to wound healing and is focused on TGF-beta and PGE2.
Katerina Akassoglou - One of the best experts on this subject based on the ideXlab platform.
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hepatic stellate cells and astrocytes stars of Scar Formation and tissue repair
Cell Cycle, 2011Co-Authors: Christian Schachtrup, Natacha Le Moan, Melissa A Passino, Katerina AkassoglouAbstract:Scar Formation inhibits tissue repair and regeneration in the liver and central nervous system. Activation of hepatic stellate cells (HSCs) after liver injury or of astrocytes after nervous system damage is considered to drive Scar Formation. HSCs are the fibrotic cells of the liver, as they undergo activation and acquire fibrogenic properties after liver injury. HSC activation has been compared to reactive gliosis of astrocytes, which acquire a reactive phenotype and contribute to Scar Formation after nervous system injury, much like HSCs after liver injury. It is intriguing that a wide range of neuroglia-related molecules are expressed by HSCs. We identified an unexpected role for the p75 neurotrophin receptor in regulating HSC activation and liver repair. Here we discuss the molecular mechanisms that regulate HSC activation and reactive gliosis and their contributions to Scar Formation and tissue repair. Juxtaposing key mechanistic and functional similarities in HSC and astrocyte activation might provide novel insight into liver regeneration and nervous system repair.
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fibrinogen triggers astrocyte Scar Formation by promoting the availability of active tgf β after vascular damage
The Journal of Neuroscience, 2010Co-Authors: Christian Schachtrup, Matthew J Helmrick, Eirini Vagena, Dennis K Galanakis, Jay L Degen, Richard U Margolis, Katerina AkassoglouAbstract:Scar Formation in the nervous system begins within hours after traumatic injury and is characterized primarily by reactive astrocytes depositing proteoglycans that inhibit regeneration. A fundamental question in CNS repair has been the identity of the initial molecular mediator that triggers glial Scar Formation. Here we show that the blood protein fibrinogen, which leaks into the CNS immediately after blood-brain barrier (BBB) disruption or vascular damage, serves as an early signal for the induction of glial Scar Formation via the TGF-β/Smad signaling pathway. Our studies revealed that fibrinogen is a carrier of latent TGF-β and induces phosphorylation of Smad2 in astrocytes that leads to inhibition of neurite outgrowth. Consistent with these findings, genetic or pharmacologic depletion of fibrinogen in mice reduces active TGF-β, Smad2 phosphorylation, glial cell activation and neurocan deposition following cortical injury. Furthermore, stereotactic injection of fibrinogen into the mouse cortex is sufficient to induce astrogliosis. Inhibition of the TGF-β receptor pathway abolishes the fibrinogen-induced effects on glial Scar Formation in vivo and in vitro. These results identify fibrinogen as a primary astrocyte activation signal, provide evidence that deposition of inhibitory proteoglycans is induced by a blood protein that leaks in the CNS after vasculature rupture, and point to TGF-β as a molecular link between vascular permeability and Scar Formation.
Peter T C So - One of the best experts on this subject based on the ideXlab platform.
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regeneration of injured skin and peripheral nerves requires control of wound contraction not Scar Formation
Wound Repair and Regeneration, 2017Co-Authors: Ioannis V Yannas, Dimitrios S Tzeranis, Peter T C SoAbstract:We review the mounting evidence that regeneration is induced in wounds in skin and peripheral nerves by a simple modification of the wound healing process. Here, the process of induced regeneration is compared to the other two well-known processes by which wounds close, i.e., contraction and Scar Formation. Direct evidence supports the hypothesis that the mechanical force of contraction (planar in skin wounds, circumferential in nerve wounds) is the driver guiding the orientation of assemblies of myofibroblasts (MFB) and collagen fibers during Scar Formation in untreated wounds. We conclude that Scar Formation depends critically on wound contraction and is, therefore, a healing process secondary to contraction. Wound contraction and regeneration did not coincide during healing in a number of experimental models of spontaneous (untreated) regeneration described in the literature. Furthermore, in other studies in which an efficient contraction-blocker, a collagen scaffold named dermis regeneration template (DRT), and variants of it, were grafted on skin wounds or peripheral nerve wounds, regeneration was systematically observed in the absence of contraction. We conclude that contraction and regeneration are mutually antagonistic processes. A dramatic change in the phenotype of MFB was observed when the contraction-blocking scaffold DRT was used to treat wounds in skin and peripheral nerves. The phenotype change was directly observed as drastic reduction in MFB density, dispersion of MFB assemblies and loss of alignment of the long MFB axes. These observations were explained by the evidence of a surface-biological interaction of MFB with the scaffold, specifically involving binding of MFB integrins α1β1 and α2β1 to ligands GFOGER and GLOGER naturally present on the surface of the collagen scaffold. In summary, we show that regeneration of wounded skin and peripheral nerves in the adult mammal can be induced simply by appropriate control of wound contraction, rather than of Scar Formation.
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.
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.
