Synthetic Retinoid Am80 Upregulates Apelin Expression by Promoting Interaction of RAR{alpha} with KLF5 and Sp1 in Vascular Smooth Muscle Cells

In this study, we investigated the molecular mechanism of apelin expression regulation by synthetic retinoid Am80 in VSMCs. The results showed that Am80 markedly upregulated apelin mRNA and protein levels in VSMCs. Furthermore, KLF5 and Sp1 cooperatively mediated Am80-induced apelin expression through their direct binding to the TGF-β control element (TCE) on the apelin promoter. Interestingly, upon Am80 stimulation, the retinoic acid receptor alpha (RARα) was recruited to the apelin promoter by interacting with KLF5 and Sp1 prebound to the TCE site of the apelin promoter to form a transcriptional activation complex, subsequently leading to the upregulation of apelin expression in VSMCs. Thus, these results describe a novel mechanism of apelin regulation by Am80 and further expand the network of RARα in the retinoid pathway.

Source: BJ Cell - August 30, 2013 Category: Biochemistry Authors: X Lv, B Zheng, S Li, A Han, C Wang, J Shi, X Zhang, Y Liu, Y Li, J Wen Tags: BJ Cell Source Type: research