Integrin ?4 in EMT: an implication of renal diseases #MMPMID26221233
Wang Q; Wang Y; Huang X; Liang W; Xiong Z; Xiong Z
Int J Clin Exp Med 2015[]; 8 (5): 6967-76 PMID26221233show ga
Renal fibrosis is a main cause of chronic renal failure. Epithelial-to-mesenchymal transition (EMT) markers play a role in renal fibrosis. Transforming growth factor-?1 (TGF-?1) has been shown to initiate and complete the whole EMT process. It is now well accepted that loss of E-cadherin, EMT marker ?-SMA, and connective tissue growth factor (CTGF) expression are key events in the EMT process. We found that by stimulating human renal proximal tubular epithelial (HK-2) cells with TGF-?1, the expression of E-cadherin was down regulated and the expression of ?-SMA and CTGF were up regulated in a dose dependent manner. In our present study we also found that integrin ?4 and peroxisome proliferators-activated receptor-? (PPAR-?) play roles in EMT process, with TGF-?1 stimulation increasing integrin ?4 expression in HK2 cells. Integrin ?4 and PPAR? were detected in tubulointerstitial tissues, immunohistochemistry analysis showed enhanced expression of integrin ?4 in early stage, with over-expression at later stage. In contrast, the expression of PPAR? showed little increased in early stage, but was dramatically decreased at later stage. This is consistent with TGF-?1 inducing EMT. Our immune-precipitation studies show that integrin ?4 disassociation with PPAR? is present in E-cadherin signaling. It suggests that PPAR? has a role in EMT inhibition.
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Int+J+Clin+Exp+Med 2015 ; 8 (5): 6967-76
