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10.1074/jbc.M116.764449 http://scihub22266oqcxt.onion/10.1074/jbc.M116.764449 C5418052!5418052!28320863     free     free     free 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       J+Biol+Chem 2017 ; 292 (18): 7542-53 Nephropedia Template TP {{tp|p=28320863|t=2017. Rac1 GTPase regulates 11? hydroxysteroid dehydrogenase type 2 and fibrotic remodeling |pdf=|usr=}}{{28320863}} gab.com Text Rac1 GTPase regulates 11 hydroxysteroid dehydrogenase type 2 and fibrotic remodeling JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=28320863 #FOAvip The aim of the study was to characterize the role of Rac1 GTPase for the mineralocorticoid receptor (MR)-mediated pro-fibrotic remodeling. Transgenic mice with cardiac overexpression of constitutively active Rac1 (RacET) develop an age-dependent phenotype with atrial dilatation, fibrosis, and atrial fibrillation. Expression of MR was similar in RacET and WT mice. The expression of 11? hydroxysteroid dehydrogenase type 2 (11?-HSD2) was age-dependently up-regulated in the atria and the left ventricles of RacET mice on mRNA and protein levels. Statin treatment inhibiting Rac1 geranylgeranylation reduced 11?-HSD2 up-regulation. Samples of human left atrial myocardium showed a positive correlation between Rac1 activity and 11?-HSD2 expression (r = 0.7169). Immunoprecipitation showed enhanced Rac1-bound 11?-HSD2 relative to Rac1 expression in RacET mice that was diminished with statin treatment. Both basal and phorbol 12-myristate 13-acetate (PMA)-induced NADPH oxidase activity were increased in RacET and correlated positively with 11?-HSD2 expression (r = 0.788 and r = 0.843, respectively). In cultured H9c2 cardiomyocytes, Rac1 activation with l-buthionine sulfoximine increased; Rac1 inhibition with NSC23766 decreased 11?-HSD2 mRNA and protein expression. Connective tissue growth factor (CTGF) up-regulation induced by aldosterone was prevented with NSC23766. Cardiomyocyte transfection with 11?-HSD2 siRNA abolished the aldosterone-induced CTGF up-regulation. Aldosterone-stimulated MR nuclear translocation was blocked by the 11?-HSD2 inhibitor carbenoxolone. In cardiac fibroblasts, nuclear MR translocation induced by aldosterone was inhibited with NSC23766 and spironolactone. NSC23766 prevented the aldosterone-induced proliferation and migration of cardiac fibroblasts and the up-regulation of CTGF and fibronectin. In conclusion, Rac1 GTPase regulates 11?-HSD2 expression, MR activation, and MR-mediated pro-fibrotic signaling. Twit Text FOAVip Rac1 GTPase regulates 11 hydroxysteroid dehydrogenase type 2 and fibrotic remodeling ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=28320863 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28320863 #FOAvip English Wikipedia <ref>{{Cite pmid|28320863}}</ref> Rac1 GTPase regulates 11? hydroxysteroid dehydrogenase type 2 and fibrotic remodeling #MMPMID28320863 Lavall D; Schuster P; Jacobs N; Kazakov A; Böhm M; Laufs U J Biol Chem 2017[May]; 292 (18): 7542-53 PMID28320863show ga The aim of the study was to characterize the role of Rac1 GTPase for the mineralocorticoid receptor (MR)-mediated pro-fibrotic remodeling. Transgenic mice with cardiac overexpression of constitutively active Rac1 (RacET) develop an age-dependent phenotype with atrial dilatation, fibrosis, and atrial fibrillation. Expression of MR was similar in RacET and WT mice. The expression of 11? hydroxysteroid dehydrogenase type 2 (11?-HSD2) was age-dependently up-regulated in the atria and the left ventricles of RacET mice on mRNA and protein levels. Statin treatment inhibiting Rac1 geranylgeranylation reduced 11?-HSD2 up-regulation. Samples of human left atrial myocardium showed a positive correlation between Rac1 activity and 11?-HSD2 expression (r = 0.7169). Immunoprecipitation showed enhanced Rac1-bound 11?-HSD2 relative to Rac1 expression in RacET mice that was diminished with statin treatment. Both basal and phorbol 12-myristate 13-acetate (PMA)-induced NADPH oxidase activity were increased in RacET and correlated positively with 11?-HSD2 expression (r = 0.788 and r = 0.843, respectively). In cultured H9c2 cardiomyocytes, Rac1 activation with l-buthionine sulfoximine increased; Rac1 inhibition with NSC23766 decreased 11?-HSD2 mRNA and protein expression. Connective tissue growth factor (CTGF) up-regulation induced by aldosterone was prevented with NSC23766. Cardiomyocyte transfection with 11?-HSD2 siRNA abolished the aldosterone-induced CTGF up-regulation. Aldosterone-stimulated MR nuclear translocation was blocked by the 11?-HSD2 inhibitor carbenoxolone. In cardiac fibroblasts, nuclear MR translocation induced by aldosterone was inhibited with NSC23766 and spironolactone. NSC23766 prevented the aldosterone-induced proliferation and migration of cardiac fibroblasts and the up-regulation of CTGF and fibronectin. In conclusion, Rac1 GTPase regulates 11?-HSD2 expression, MR activation, and MR-mediated pro-fibrotic signaling. äRac1 GTPase regulates 11? hydroxysteroid dehydrogenase type 2 and fibr(epmc).pdf DeepDyve Pubget Overpricing