Protective effect of retinoic acid receptor α on hypoxia-induced epithelial to mesenchymal transition of renal tubular epithelial cells associated with TGF-β/MMP-9 pathway.
Retinoic acid receptor α (RARα), 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 RARα 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 RARα in hypoxia-induced EMT of renal tubular epithelial cells (RTECs). Our results showed that expression of RARα 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 α-smooth muscle actin (α-SMA) and vimentin, in accord with EMT. Meanwhile, hypoxia could cause RTECs to obviously express TGF-β and matrix metalloproteinase-9 (MMP-9). Furthermore, using lentivirus-based delivery vectors to overexpress RARα in RTECs, we demonstrated that RARα alleviated hypoxia-induced EMT of RTECs and downregulated the expression levels of TGF-β and MMP-9. In a word, RARα protects RTECs against EMT induced by hypoxia associated with TGF-β/MMP-9 pathway.
['Gong|Ling|L|', 'Jiang|Ling|L|', 'Qin|Yuanhan|Y|', 'Jiang|Xingbo|X|', 'Song|Kunling|K|', 'Yu|Xueyun|X|']
D000818:Animals D015820:Cadherins D015687:Cell Hypoxia D002460:Cell Line D015536:Down-Regulation D004847:Epithelial Cells D058750:Epithelial-Mesenchymal Transition D007687:Kidney Tubules, Proximal D020780:Matrix Metalloproteinase 9 D051381:Rats D000072482:Retinoic Acid Receptor alpha D015398:Signal Transduction D016212:Transforming Growth Factor beta D014746:Vimentin
retinoic acid receptor α epithelial to mesenchymal transition renal tubular epithelial cells TGF-β hypoxia matrix metalloproteinase-9