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10.1152/ajprenal.00589.2014 http://scihub22266oqcxt.onion/10.1152/ajprenal.00589.2014 C4422350!4422350!25477471     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 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 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 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 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Am+J+Physiol+Renal+Physiol 2015 ; 308 (5): F425-36 Nephropedia Template TP {{tp|p=25477471|t=2015. Cyclic stretch-induced TGF-?1 and fibronectin expression is mediated by ?1-integrin through c-Src- and STAT3-dependent pathways in renal epithelial cells |pdf=|usr=}}{{25477471}} gab.com Text Cyclic stretch-induced TGF- 1 and fibronectin expression is mediated by 1-integrin through c-Src- and STAT3-dependent pathways in renal epithelial cells JO: Am J Physiol Renal Physiol http://www.kidney.de/pget.php?&tw=1&pmid=25477471 #FOAvip Extracellular matrix (ECM) proteins, including fibronectin, may contribute to the early development and progression of renal interstitial fibrosis associated with chronic renal disease. Recent studies showed that ?1-integrin is associated with the development of renal fibrosis in a murine model of unilateral ureteral obstruction (UUO). However, the molecular events responsible for ?1-integrin-mediated signaling, following UUO, have yet to be determined. In this study, we investigated the mechanism by which mechanical stretch, an in vitro model for chronic obstructive nephropathy, regulates fibronectin and transforming growth factor-?1 (TGF-?1) expression in cultured human proximal tubular epithelium (HK-2) cells. Mechanical stretch upregulated fibronectin and TGF-?1 expression and activated signal transducer and transcription factor 3 (STAT3) in a time-dependent manner. Stretch-induced fibronectin and TGF-?1 were suppressed by a STAT3 inhibitor, S3I-201, and by small interfering RNA (siRNA) targeting human STAT3 (STAT3 siRNA). Similarly, fibronectin and TGF-?1 expression and STAT3 activation induced by mechanical stretch were suppressed by the Src family kinase inhibitor PP2 and by transfection of HK-2 cells with a dominant-negative mutant of c-Src (DN-Src), whereas PP3, an inactive analog of PP2, had no significant effect. Furthermore, mechanical stretch resulted in increased ?1-integrin mRNA and protein levels in HK-2 cells. Furthermore, neutralizing antibody against ?1-integrin and silencing of ?1-integrin expression with siRNAs resulted in decreased c-Src and STAT3 activation and TGF-?1 and fibronectin expression evoked by mechanical stretch. This work demonstrates, for the first time, a role for ?1-integrin in stretch-induced renal fibrosis through the activation of c-Src and STAT3 signaling pathways. Twit Text FOAVip Cyclic stretch-induced TGF- 1 and fibronectin expression is mediated by 1-integrin through c-Src- and STAT3-dependent pathways in renal epithelial cells ????Am J Physiol Renal Physiol http://www.kidney.de/pget.php?&tw=1&pmid=25477471 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25477471 #FOAvip English Wikipedia <ref>{{Cite pmid|25477471}}</ref> Cyclic stretch-induced TGF-?1 and fibronectin expression is mediated by ?1-integrin through c-Src- and STAT3-dependent pathways in renal epithelial cells #MMPMID25477471 Hamzeh MT; Sridhara R; Alexander LD Am J Physiol Renal Physiol 2015[Mar]; 308 (5): F425-36 PMID25477471show ga Extracellular matrix (ECM) proteins, including fibronectin, may contribute to the early development and progression of renal interstitial fibrosis associated with chronic renal disease. Recent studies showed that ?1-integrin is associated with the development of renal fibrosis in a murine model of unilateral ureteral obstruction (UUO). However, the molecular events responsible for ?1-integrin-mediated signaling, following UUO, have yet to be determined. In this study, we investigated the mechanism by which mechanical stretch, an in vitro model for chronic obstructive nephropathy, regulates fibronectin and transforming growth factor-?1 (TGF-?1) expression in cultured human proximal tubular epithelium (HK-2) cells. Mechanical stretch upregulated fibronectin and TGF-?1 expression and activated signal transducer and transcription factor 3 (STAT3) in a time-dependent manner. Stretch-induced fibronectin and TGF-?1 were suppressed by a STAT3 inhibitor, S3I-201, and by small interfering RNA (siRNA) targeting human STAT3 (STAT3 siRNA). Similarly, fibronectin and TGF-?1 expression and STAT3 activation induced by mechanical stretch were suppressed by the Src family kinase inhibitor PP2 and by transfection of HK-2 cells with a dominant-negative mutant of c-Src (DN-Src), whereas PP3, an inactive analog of PP2, had no significant effect. Furthermore, mechanical stretch resulted in increased ?1-integrin mRNA and protein levels in HK-2 cells. Furthermore, neutralizing antibody against ?1-integrin and silencing of ?1-integrin expression with siRNAs resulted in decreased c-Src and STAT3 activation and TGF-?1 and fibronectin expression evoked by mechanical stretch. This work demonstrates, for the first time, a role for ?1-integrin in stretch-induced renal fibrosis through the activation of c-Src and STAT3 signaling pathways. äCyclic stretch-induced TGF-?1 and fibronectin expression is mediated b(epmc).pdf DeepDyve Pubget Overpricing