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10.1097/01.MIB.0000437615.98881.31 http://scihub22266oqcxt.onion/10.1097/01.MIB.0000437615.98881.31 C4893808!4893808!24280883     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\24280883.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Inflamm+Bowel+Dis 2014 ; 20 (1): 154-65 Nephropedia Template TP {{tp|p=24280883|t=2014. Novel Rho/MRTF/SRF Inhibitors Block Matrix-stiffness and TGF-??Induced Fibrogenesis in Human Colonic Myofibroblasts |pdf=|usr=}}{{24280883}} gab.com Text Novel Rho/MRTF/SRF Inhibitors Block Matrix-stiffness and TGF- Induced Fibrogenesis in Human Colonic Myofibroblasts JO: Inflamm Bowel Dis http://www.kidney.de/pget.php?&tw=1&pmid=24280883 #FOAvip Background: Ras homolog gene family, member A (RhoA)/Rho-associated coiled-coil forming protein kinase signaling is a key pathway in multiple types of solid organ fibrosis, including intestinal fibrosis. However, the pleiotropic effects of RhoA/Rho-associated coiled-coil forming protein kinase signaling have frustrated targeted drug discovery efforts. Recent recognition of the role of Rho-regulated gene transcription by serum response factor (SRF) and its transcriptional cofactor myocardin-related transcription factor A (MRTF-A) suggest a novel locus for pharmacological intervention. Methods: Because RhoA signaling is mediated by both physical and biochemical stimuli, we examined whether pharmacological inhibition of RhoA or the downstream transcription pathway of MRTF-A/SRF could block intestinal fibrogenesis in 2 in vitro models. Results: In this study, we demonstrate that inhibition of RhoA signaling blocks both matrix-stiffness and transforming growth factor beta?induced fibrogenesis in human colonic myofibroblasts. Repression of alpha-smooth muscle actin and collagen expression was associated with the inhibition of MRTF-A nuclear localization. CCG-1423, a first-generation Rho/MRTF/SRF pathway inhibitor, repressed fibrogenesis in both models, yet has unacceptable cytotoxicity. Novel second-generation inhibitors (CCG-100602 and CCG-203971) repressed both matrix-stiffness and transforming growth factor beta?mediated fibrogenesis as determined by protein and gene expression in a dose-dependent manner. Conclusions: Targeting the Rho/MRTF/SRF mechanism with second-generation Rho/MRTF/SRF inhibitors may represent a novel approach to antifibrotic therapeutics. Twit Text FOAVip Novel Rho/MRTF/SRF Inhibitors Block Matrix-stiffness and TGF- Induced Fibrogenesis in Human Colonic Myofibroblasts ????Inflamm Bowel Dis http://www.kidney.de/pget.php?&tw=1&pmid=24280883 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24280883 #FOAvip English Wikipedia <ref>{{Cite pmid|24280883}}</ref> Novel Rho/MRTF/SRF Inhibitors Block Matrix-stiffness and TGF-??Induced Fibrogenesis in Human Colonic Myofibroblasts #MMPMID24280883 Johnson LA; Rodansky ES; Haak AJ; Larsen SD; Neubig RR; Higgins PDR Inflamm Bowel Dis 2014[Jan]; 20 (1): 154-65 PMID24280883show ga Background: Ras homolog gene family, member A (RhoA)/Rho-associated coiled-coil forming protein kinase signaling is a key pathway in multiple types of solid organ fibrosis, including intestinal fibrosis. However, the pleiotropic effects of RhoA/Rho-associated coiled-coil forming protein kinase signaling have frustrated targeted drug discovery efforts. Recent recognition of the role of Rho-regulated gene transcription by serum response factor (SRF) and its transcriptional cofactor myocardin-related transcription factor A (MRTF-A) suggest a novel locus for pharmacological intervention. Methods: Because RhoA signaling is mediated by both physical and biochemical stimuli, we examined whether pharmacological inhibition of RhoA or the downstream transcription pathway of MRTF-A/SRF could block intestinal fibrogenesis in 2 in vitro models. Results: In this study, we demonstrate that inhibition of RhoA signaling blocks both matrix-stiffness and transforming growth factor beta?induced fibrogenesis in human colonic myofibroblasts. Repression of alpha-smooth muscle actin and collagen expression was associated with the inhibition of MRTF-A nuclear localization. CCG-1423, a first-generation Rho/MRTF/SRF pathway inhibitor, repressed fibrogenesis in both models, yet has unacceptable cytotoxicity. Novel second-generation inhibitors (CCG-100602 and CCG-203971) repressed both matrix-stiffness and transforming growth factor beta?mediated fibrogenesis as determined by protein and gene expression in a dose-dependent manner. Conclusions: Targeting the Rho/MRTF/SRF mechanism with second-generation Rho/MRTF/SRF inhibitors may represent a novel approach to antifibrotic therapeutics. äNovel Rho/MRTF/SRF Inhibitors Block Matrix-stiffness and TGF-??Induced(epmc).pdf DeepDyve Pubget Overpricing