title: Integrin β4 in EMT: an implication of renal diseases.
abstract: 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-β1 (TGF-β1) has been shown to initiate and complete the whole EMT process. It is now well accepted that loss of E-cadherin, EMT marker α-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-β1, the expression of E-cadherin was down regulated and the expression of α-SMA and CTGF were up regulated in a dose dependent manner. In our present study we also found that integrin β4 and peroxisome proliferators-activated receptor-γ (PPAR-γ) play roles in EMT process, with TGF-β1 stimulation increasing integrin β4 expression in HK2 cells. Integrin β4 and PPARγ were detected in tubulointerstitial tissues, immunohistochemistry analysis showed enhanced expression of integrin β4 in early stage, with over-expression at later stage. In contrast, the expression of PPARγ showed little increased in early stage, but was dramatically decreased at later stage. This is consistent with TGF-β1 inducing EMT. Our immune-precipitation studies show that integrin β4 disassociation with PPARγ is present in E-cadherin signaling. It suggests that PPARγ has a role in EMT inhibition.
authors.affiliation: Department of Nephrology, Peking University Shenzhen Hospital Shenzhen 518036, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Peking University Shenzhen Hospital Shenzhen 518036, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Peking University Shenzhen Hospital Shenzhen 518036, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Nephrology, Peking University Shenzhen Hospital Shenzhen 518036, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Nephrology, Peking University Shenzhen Hospital Shenzhen 518036, China.
authors.forename: Zibo
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Department of Nephrology, Peking University Shenzhen Hospital Shenzhen 518036, China.
authors.forename: Zuying
authors.initials: Z
authors.lastname: Xiong
keywords: EMT; Integrin β4; PPARγ; renal diseases