Protective effect of retinoic acid receptor on hypoxia-induced epithelial to mesenchymal transition of renal tubular epithelial cells associated with TGF-/MMP-9 pathway

Retinoic acid receptor (RAR), a member of family of the nuclear retinoic acid receptors (RARs), plays an essential role in various chronic kidney diseases (CKD). Renal tubular epithelial to mesenchymal transition (EMT) is a common mechanism of progression of renal interstitial fibrosis (RIF). Hypoxia has been extensively considered as one of major inducers of renal tubular EMT. However, the effects of RAR on hypoxia-induced EMT have not yet been described so far. The aim of the present study was to explore the roles and potential mechanisms of RAR in hypoxia-induced EMT of renal tubular epithelial cells (RTECs). Our results showed that expression of RAR in RTECs subjected to hypoxia significantly was reduced, accompanied by decreased expression level of the epithelial marker E-cadherin, and increased expression levels of the mesenchymal markers -smooth muscle actin (-SMA) and vimentin, in accord with EMT. Meanwhile, hypoxia could cause RTECs to obviously express TGF- and matrix metalloproteinase-9 (MMP-9). Furthermore, using lentivirus-based delivery vectors to overexpress RAR in RTECs, we demonstrated that RAR alleviated hypoxia-induced EMT of RTECs and downregulated the expression levels of TGF- and MMP-9. In a word, RAR protects RTECs against EMT induced by hypoxia associated with TGF-/MMP-9 pathway.