Effect of Rosiglitazone on the Epithelial-mesenchymal Transition Process of Renal Tubu-lar Epithelial Cell / 医药导报

ABSTRACT

Objective To investigate the effect of rosiglitazone on the epithelial-mesenchymal transition process of renal tubular epithelial cell induced by transforming growth factor-β(TGF-β). Methods The human renal tubular epithelial cell line HK-2 was cultured in vitro and treated with TGF-β at the presence or absence of rosiglitazone, and the morphological changes of HK-2 cells were observed. Then PPARγ,SMAD family number 2/ 3,E-cadherin and Vimentin were detected by western blot, and the mRNA expression of PPARγ, E-cadherin, Vimentin, zinc finger transcription factor Snail and Slug were measured by realtime quantitative PCR. Finally,dual luciferase reporter assay was performed to detect the effect of TGF-β and rosiglitazone on the tran-scription activity of E-cadherin promoter. Results TGF-β could induce the EMT process of HK-2, including morphological changes such as longer pseudopod and broader cell space. TGF-β also activated the SMAD2/ 3 signaling pathway, with expression changes of E-cadherin and Vimentin. Rosiglitazone reversed the morphological changes of HK-2 cells induced by TGF-β, with shor-ter pseudopod and narrower cell space. Rosiglitazone also inhibited the mRNA and protein expressions of Vimentin, and restored the mRNA and protein expression of E-cadherin by up-regulating PPARγ. The activity of E-cadherin promoter was enhanced under the treatment of rosiglitazone. Conclusion Rosiglitazone can antagonize the EMT process of renal tubular epithelial cell induced by TGF-β, through the activation of PPARγ and stimulating transcription and protein expression of E-cadherin.