Src inhibition blocks renal interstitial fibroblast activation and ameliorates renal fibrosis.
作者： Yanli Yan , Li Ma , Xiaoxu Zhou , Murugavel Ponnusamy , Jinhua Tang
DOI: 10.1038/KI.2015.293
关键词:
摘要: Increased Src activity has been associated with the pathogenesis of renal tumors and some glomerular diseases, but its role in interstitial fibrosis remains elusive. To evaluate this, cultured fibroblasts (NRK-49F) were treated PP1, a selective inhibitor Src. This resulted decreased expression α-smooth muscle actin, fibronectin, collagen I response to serum, angiotension II, or transforming growth factor-β1 (TGF-β1). Silencing siRNA also inhibited those proteins. Furthermore, inhibition blocked fibroblast proliferation. In murine model induced by unilateral ureteral obstruction, active form (phopsho-Src Tyr416) was upregulated both tubular cells fibrotic kidney. Its inactivation reduced activation attenuated extracellular matrix protein deposition. suppressed TGF-β1 signaling, epidermal factor receptor STAT3, number epithelial arrested at G2/M phase cell cycle after obstruction. Thus, is an important mediator fibrosis, we suggest that potential therapeutic target for treatment chronic fibrosis.
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