GPR30 decreases with vascular aging and promotes vascular smooth muscle cells maintaining differentiated phenotype and suppressing migration via activation of ERK1/2

Abstract

Fang Huang,1,2 Jianguo Yin,2 Keyu Li,1 Ying Li,1 Heng Qi,1 Li Fang,1 Cong Yuan,1 Weiwei Liu,1 Min Wang,2 Xiangping Li2 1Department of Cardiology, The First Hospital of Changsha, 2Department of Cardiology, The Second XiangYa Hospital of Central South University, Changsha, Hunan Province, People’s Republic of China Abstract: Estrogen receptors, including classic nuclear receptors ERα, ERβ, and membrane receptor GPR30, are expressed in vascular tissues and exert protective actions in vascular diseases. But the expression pattern and functional roles of GPR30 in vascular smooth muscle cells (VSMCs) remain unclear. In this study, we found that ERα, ERβ, and GPR30 were decreased with VSMCs passaging in vitro or growing in vivo and activation of GPR30 promoted ERα expression. Then, we validated that activation of GPR30 significantly decreased migratory capability of VSMCs and suppressed ERα, whereas PDGF-BB (20 ng/mL) treatment caused increase of migration. And activation of GPR30 led to reduction of osteopontin and cellular retinol binding protein 1, enhancement of calponin and 3F8, and upregulation of total and phosphorylated ERK1/2 expression in VSMCs knocked down by GPR30, ERα, and ERβ or treated with PDGF-BB. These data suggest that GPR30 promotes VSMCs reducing migration and maintaining differentiated phenotype via activation of ERK1/2 pathway. Our findings provide novel mechanisms of GPR30 protection of VSMCs as well as a new target for prevention of vascular aging. Keywords: vascular smooth muscle cell, estrogen receptor, G protein-coupled receptor 30, phenotype, migration

Keywords

• Vascular smooth muscle cell
• Estrogen receptor
• G protein-coupled receptor 30
• Phenotype
• Migration