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10.1186/s13075-015-0754-7 http://scihub22266oqcxt.onion/10.1186/s13075-015-0754-7 C4566861!4566861 !26357964     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 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\26357964 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Arthritis+Res+Ther 2015 ; 17 (1 ): 247 Nephropedia Template TP {{tp|p=26357964 |t=2015. Macitentan inhibits the transforming growth factor-? profibrotic action, blocking the signaling mediated by the ETR/T?RI complex in systemic sclerosis dermal fibroblasts |pdf=|usr=}}{{26357964 }} gab.com Text Macitentan inhibits the transforming growth factor- profibrotic action, blocking the signaling mediated by the ETR/T RI complex in systemic sclerosis dermal fibroblasts JO: Arthritis Res Ther http://www.kidney.de/pget.php?&tw=1&pmid=26357964 #FOAvip INTRODUCTION: Systemic sclerosis (SSc) is a complex and not fully understood autoimmune disease associated with fibrosis of multiple organs. The main effector cells, the myofibroblasts, are collagen-producing cells derived from the activation of resting fibroblasts. This process is regulated by a complex repertoire of profibrotic cytokines, and among them transforming growth factor beta (TGF-?) and endothelin-1 (ET-1) play a major role. In this paper we show that TGF-? and ET-1 receptors co-operate in myofibroblast activation, and macitentan, an ET-1 receptor antagonist binding ET-1 receptors, might interfere with both TGF-? and ET-1 pathways, preventing myofibroblast differentiation. METHODS: Fibroblasts isolated from healthy controls and SSc patients were treated with TGF-? and ET-1 and successively analyzed for alpha smooth muscle actin (?-SMA) and collagen (Col1A1) expression and for the Sma and Mad Related (SMAD) phosphorylation. We further tested the ability of macitentan to interfere with these process. Furthermore, we silenced ET-1 and endothelin-1 receptor A expression and evaluated the formation of an ET-1/TGF-? receptor complex by immunoprecitation assay. RESULTS: We showed myofibroblast activation in SSc fibroblasts assessing the expression of ?-SMA and Col1A1, after stimulation with TGF-? and ET-1. Macitentan interfered with both ET-1- and TGF-?-induced fibroblast activation. To explain this unexpected inhibitory effect of macitentan on TGF-? activity, we silenced ET-1 expression on SSc fibroblasts and co-immunoprecipitated these two receptors, showing the formation of an ET-1/TGF-? receptor complex. CONCLUSIONS: During SSc, ET-1 produced by activated endothelia contributes to myofibroblast activation using TGF-? machinery via an ET-1/TGF-? receptor complex. Macitentan interferes with the profibrotic action of TGF-?, blocking the ET-1 receptor portion of the ET-1/TGF-? receptor complex. Twit Text FOAVip Macitentan inhibits the transforming growth factor- profibrotic action, blocking the signaling mediated by the ETR/T RI complex in systemic sclerosis dermal fibroblasts ????Arthritis Res Ther http://www.kidney.de/pget.php?&tw=1&pmid=26357964 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26357964 #FOAvip English Wikipedia <ref>{{Cite pmid|26357964 }}</ref> Macitentan inhibits the transforming growth factor-? profibrotic action, blocking the signaling mediated by the ETR/T?RI complex in systemic sclerosis dermal fibroblasts #MMPMID26357964 Cipriani P ; Di Benedetto P ; Ruscitti P ; Verzella D ; Fischietti M ; Zazzeroni F ; Liakouli V ; Carubbi F ; Berardicurti O ; Alesse E ; Giacomelli R Arthritis Res Ther 2015[Sep]; 17 (1 ): 247 PMID26357964 show ga INTRODUCTION: Systemic sclerosis (SSc) is a complex and not fully understood autoimmune disease associated with fibrosis of multiple organs. The main effector cells, the myofibroblasts, are collagen-producing cells derived from the activation of resting fibroblasts. This process is regulated by a complex repertoire of profibrotic cytokines, and among them transforming growth factor beta (TGF-?) and endothelin-1 (ET-1) play a major role. In this paper we show that TGF-? and ET-1 receptors co-operate in myofibroblast activation, and macitentan, an ET-1 receptor antagonist binding ET-1 receptors, might interfere with both TGF-? and ET-1 pathways, preventing myofibroblast differentiation. METHODS: Fibroblasts isolated from healthy controls and SSc patients were treated with TGF-? and ET-1 and successively analyzed for alpha smooth muscle actin (?-SMA) and collagen (Col1A1) expression and for the Sma and Mad Related (SMAD) phosphorylation. We further tested the ability of macitentan to interfere with these process. Furthermore, we silenced ET-1 and endothelin-1 receptor A expression and evaluated the formation of an ET-1/TGF-? receptor complex by immunoprecitation assay. RESULTS: We showed myofibroblast activation in SSc fibroblasts assessing the expression of ?-SMA and Col1A1, after stimulation with TGF-? and ET-1. Macitentan interfered with both ET-1- and TGF-?-induced fibroblast activation. To explain this unexpected inhibitory effect of macitentan on TGF-? activity, we silenced ET-1 expression on SSc fibroblasts and co-immunoprecipitated these two receptors, showing the formation of an ET-1/TGF-? receptor complex. CONCLUSIONS: During SSc, ET-1 produced by activated endothelia contributes to myofibroblast activation using TGF-? machinery via an ET-1/TGF-? receptor complex. Macitentan interferes with the profibrotic action of TGF-?, blocking the ET-1 receptor portion of the ET-1/TGF-? receptor complex. |Actins/metabolism [MESH] |Adult [MESH] |Blotting, Western [MESH] |Collagen Type I, alpha 1 Chain [MESH] |Collagen Type I/metabolism [MESH] |Dermis/pathology [MESH] |Endothelin A Receptor Antagonists/pharmacology [MESH] |Endothelin-1/pharmacology [MESH] |Female [MESH] |Fibroblasts/*drug effects/metabolism [MESH] |Humans [MESH] |Male [MESH] |Middle Aged [MESH] |Multiprotein Complexes/metabolism [MESH] |Phosphorylation/drug effects [MESH] |Pyrimidines/*pharmacology [MESH] |RNA Interference [MESH] |Receptor, Endothelin A/genetics/*metabolism [MESH] |Receptors, Transforming Growth Factor beta/*metabolism [MESH] |Scleroderma, Systemic/metabolism/pathology [MESH] |Signal Transduction/drug effects [MESH] |Smad Proteins/metabolism [MESH] |Sulfonamides/*pharmacology [MESH] |Transforming Growth Factor beta1/*pharmacology [MESH] |Up-Regulation/drug effects [MESH]Macitentan inhibits the transforming growth factor-? profibrotic actio(epmc).pdf DeepDyve Pubget Overpricing