FXR-mediated regulation of angiotensin type 2 receptor expression in vascular smooth muscle cells

摘要: Aims The farnesoid X receptor (FXR) is a member of the nuclear superfamily and plays an important role in pathogenesis cardiovascular diseases via regulating metabolism transport cholesterol. We others have recently shown that FXR also expressed vasculature, including endothelial cells smooth muscle (SMC). However, biological significance activation SMC still poorly understood. In this study, we examine effect ligands on angiotensin system rat aortic (RASMC), as II (Ang II) signalling contributes to various types vascular lesions by promoting cell growth SMC. Methods results Treatment RASMC with ligand showed no obvious expression angiotensinogen, Ang type 1 (AT1R) or 4 (AT4R) but led significant increase 2 (AT2R). treatment resulted inhibition II-mediated extracellular signal-regulated kinase (ERK) proliferation. Promoter reporter gene electrophoretic mobility-shift assays suggest upregulates AT2R at transcriptional level. Upregulation appears play FXR-mediated ERK upregulation Rous sarcoma oncogene (Src) homology domain-containing tyrosine phosphatase (SHP-1) because SHP-1 can be blocked antagonist inactivation was significantly attenuated either inhibitor. Conclusion may serve novel molecular target for modulating vasculature.