Jagged-1/Notch3 signaling transduction pathway is involved in apelin-13-induced vascular smooth muscle cells proliferation.

The apelin/apelin receptor (APJ, apelin-angiotensin receptor-like 1) system is a newly deorphanized G protein-coupled receptor system. Both apelin and APJ that are important regulatory factors are expressed in the cardiovascular system. Our previous studies demonstrated that apelin-13 significantly stimulated vascular smooth muscle cell (VSMC) proliferation. In this paper, our data suggested that the Jagged-1/Notch3 signaling transduction pathway is involved in apelin-13-induced VSMC proliferation by promoting the expression of Cyclin D1. Results indicated that apelin-13 stimulates the proliferation of VSMC and the expression of Jagged-1 and Notch3 in concentration- and time-dependent manners. The increased expression of Jagged-1 and Notch3 induced by apelin-13 could be abolished by extracellular signal-regulated protein kinase (ERK) blockade. PD98059 (ERK inhibitor) can inhibit the activation of Jagged-1/Notch3 induced by apelin-13. Down-regulation of Notch3 using small interfering RNA inhibits the expression of Cyclin D1 and prevents apelin-13-induced VSMC proliferation. In conclusion, Jagged-1/Notch3 signaling transduction pathway is involved in VSMC proliferation induced by apelin-13.