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10.1016/j.taap.2014.08.006 http://scihub22266oqcxt.onion/10.1016/j.taap.2014.08.006 25150141!ä!25150141 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Toxicol+Appl+Pharmacol 2014 ; 280 (2): 335-44 Nephropedia Template TP {{tp|p=25150141|t=2014. TGF-beta1-elevated TRPM7 channel regulates collagen expression in hepatic stellate cells via TGF-beta1/Smad pathway |pdf=|usr=}}{{25150141}} gab.com Text TGF-beta1-elevated TRPM7 channel regulates collagen expression in hepatic stellate cells via TGF-beta1/Smad pathway JO: Toxicol Appl Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=25150141 #FOAvip Transdifferentiation of hepatic stellate cells (HSCs) into myofibroblasts plays a critical role in the development of liver fibrosis, since myofibroblasts are the key cells responsible for excessive deposition of ECM proteins. Transient receptor potential melastatin 7 (TRPM7), a non-selective cation channel with protein serine/threonine kinase activity, has been demonstrated to function in the proliferation of activated HSCs. Here, we investigated the functional role of TRPM7 in collagen deposition in activated HSC-T6 cells (a rat hepatic stellate cell line). TRPM7 mRNA and protein were measured by Real-time PCR and Western blot in TGF-beta1-activated HSC-T6 cells in vitro. Results demonstrated that TRPM7 protein was dramatically increased in fibrotic human livers. Stimulation of HSC-T6 cells with TGF-beta1 increased TRPM7 mRNA and protein level in a time-dependent manner. Nevertheless, TGF-beta1-elicited upregulation of TRPM7 in HSC-T6 cells was abrogated by SB431542 (TGF-beta1 receptor blocker) or SIS3 (inhibitor of Smad3 phosphorylation). Additionally, blockade of TRPM7 channels with non-specific TRPM7 blocker 2-APB or synthetic siRNA targeting TRPM7 attenuated TGF-beta1-induced expression of myofibroblast markers, as measured by the induction of alpha-SMA and Col1alpha1. Silencing TRPM7 also increased the ratio of MMPs/TIMPs by increasing MMP-13 expression and decreasing TIMP-1 and TIMP-2 levels. Strikingly, phosphorylation of p-Smad2 and p-Smad3, associated with collagen production, was decreased in TRPM7 deficient HSC-T6 cells. These observations suggested that TGF-beta1 elevates TRPM7 expression in HSCs via Smad3-dependant mechanisms, which in turn contributes Smad protein phosphorylation, and subsequently increases fibrous collagen expression. Therefore, TRPM7 may constitute a useful target for the treatment of liver fibrosis. Twit Text FOAVip TGF-beta1-elevated TRPM7 channel regulates collagen expression in hepatic stellate cells via TGF-beta1/Smad pathway ????Toxicol Appl Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=25150141 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25150141 #FOAvip English Wikipedia <ref>{{Cite pmid|25150141}}</ref> TGF-beta1-elevated TRPM7 channel regulates collagen expression in hepatic stellate cells via TGF-beta1/Smad pathway #MMPMID25150141 Fang L; Huang C; Meng X; Wu B; Ma T; Liu X; Zhu Q; Zhan S; Li J Toxicol Appl Pharmacol 2014[Oct]; 280 (2): 335-44 PMID25150141show ga Transdifferentiation of hepatic stellate cells (HSCs) into myofibroblasts plays a critical role in the development of liver fibrosis, since myofibroblasts are the key cells responsible for excessive deposition of ECM proteins. Transient receptor potential melastatin 7 (TRPM7), a non-selective cation channel with protein serine/threonine kinase activity, has been demonstrated to function in the proliferation of activated HSCs. Here, we investigated the functional role of TRPM7 in collagen deposition in activated HSC-T6 cells (a rat hepatic stellate cell line). TRPM7 mRNA and protein were measured by Real-time PCR and Western blot in TGF-beta1-activated HSC-T6 cells in vitro. Results demonstrated that TRPM7 protein was dramatically increased in fibrotic human livers. Stimulation of HSC-T6 cells with TGF-beta1 increased TRPM7 mRNA and protein level in a time-dependent manner. Nevertheless, TGF-beta1-elicited upregulation of TRPM7 in HSC-T6 cells was abrogated by SB431542 (TGF-beta1 receptor blocker) or SIS3 (inhibitor of Smad3 phosphorylation). Additionally, blockade of TRPM7 channels with non-specific TRPM7 blocker 2-APB or synthetic siRNA targeting TRPM7 attenuated TGF-beta1-induced expression of myofibroblast markers, as measured by the induction of alpha-SMA and Col1alpha1. Silencing TRPM7 also increased the ratio of MMPs/TIMPs by increasing MMP-13 expression and decreasing TIMP-1 and TIMP-2 levels. Strikingly, phosphorylation of p-Smad2 and p-Smad3, associated with collagen production, was decreased in TRPM7 deficient HSC-T6 cells. These observations suggested that TGF-beta1 elevates TRPM7 expression in HSCs via Smad3-dependant mechanisms, which in turn contributes Smad protein phosphorylation, and subsequently increases fibrous collagen expression. Therefore, TRPM7 may constitute a useful target for the treatment of liver fibrosis. |*Signal Transduction/physiology[MESH] |Actins/analysis[MESH] |Animals[MESH] |Collagen Type I, alpha 1 Chain[MESH] |Collagen Type I/analysis[MESH] |Collagen/*metabolism[MESH] |Hepatic Stellate Cells/*metabolism[MESH] |Male[MESH] |Rats[MESH] |Rats, Sprague-Dawley[MESH] |Smad Proteins/*physiology[MESH] |TRPM Cation Channels/analysis/antagonists & inhibitors/*physiology[MESH]TGF-beta1-elevated TRPM7 channel regulates collagen expression in hepa(epmc).pdf DeepDyve Pubget Overpricing