Department of Microbiology and Immunology, University of South China, Hengyang 421001, China.
Acta Biochim Biophys Sin (Shanghai). 2013 Oct;45(10):875-81. doi: 10.1093/abbs/gmt085. Epub 2013 Aug 6.
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.
Apelin/apelin receptor (APJ, apelin-angiotensin receptor-like 1) 系统是一个新的孤儿 G 蛋白偶联受体系统。Apelin 和 APJ 都是重要的调节因子，它们在心血管系统中表达。我们之前的研究表明，apelin-13 可显著刺激血管平滑肌细胞（VSMC）增殖。在本文中，我们的数据表明 Jagged-1/Notch3 信号转导通路通过促进 Cyclin D1 的表达参与了 apelin-13 诱导的 VSMC 增殖。结果表明，apelin-13 以浓度和时间依赖的方式刺激 VSMC 增殖和 Jagged-1 和 Notch3 的表达。apelin-13 诱导的 Jagged-1 和 Notch3 的表达增加可被细胞外信号调节蛋白激酶（ERK）阻断所消除。PD98059（ERK 抑制剂）可抑制 apelin-13 诱导的 Jagged-1/Notch3 的激活。使用小干扰 RNA 下调 Notch3 可抑制 Cyclin D1 的表达并阻止 apelin-13 诱导的 VSMC 增殖。总之，Jagged-1/Notch3 信号转导通路参与了 apelin-13 诱导的 VSMC 增殖。
