【摘 要】
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The nuclear transcription factor signal transducer and activator of transcription 3 (STAT3) plays a significant role in cell cycling and proliferation.STAT3 is activated via phosphorylation by Janus k
【机 构】
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Department of Physiology and Pathophysiology,Shanghai Medical College,Fudan University,Shanghai 2000
【出 处】
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International Conference for Physiological Sciences 2012(201
论文部分内容阅读
The nuclear transcription factor signal transducer and activator of transcription 3 (STAT3) plays a significant role in cell cycling and proliferation.STAT3 is activated via phosphorylation by Janus kinase2 (JAK2)and acetylation by histone acetyltransferase p300/CBR It was recently noticed that STAT3 signaling pathway was involved in regulating the genes that contribute to renal interstitial fibrosis.Previous studies have demonstrated that tyrosine kinases mediate angiotensin Ⅱ (Ang Ⅱ) effects in different cell types, but the association between AngⅡ-JAK2-STAT3 pathway and renal interstitial fibrosis is uncertain.In this study, we explore the correlate between STAT3 signaling and renal interstitial fibrosis in cultured renal tubular epithelial cells.Western blot was used to evaluate the STAT3 acetylation and phosphorylation, as well as collagen Ⅳ, fibronectin and TGF-β1 protein levels.Transfection of recombinant palsmid vector carrying p300 gene was used to upregulate p300 expression.P300 siRNA was used to knockdown the p300 expression.The results showed that Ang Ⅱ increased STAT3 phosphorylation at Try705, TGF-β1, collagen Ⅳ and fibronectin expressions in renal tubular epithelial cells.These effects were blocked by curcumin, an inhibitor of JAK2 and p300/CBP.The inhibition of STAT3 acetylation at Lys685 by C646, p300siRNA and resveratrol decreased Ang Ⅱ-induced STAT3 phosphorylation at Try705, and TGF-31, collagen Ⅳ and fibronectin expressions.P300 up-regulated the basal level of STAT3 acetylation and enhanced Ang Ⅱ-induced STAT3 phosphorylation and relevant downstream protein expressions.These result suggested that the STAT3 acetylation is necessary for Ang Ⅱ-induced STAT3 phosphorylation and consequent extracellular matrix protein synthesis.
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