NOX4-Derived Reactive Oxygen Species Drive Apelin-13-Induced Vascular Smooth Muscle Cell Proliferation via the ERK Pathway |
| |
Authors: | Lanfang Li Fang Li Feng Li Xiaohuan Mao Li Yang Hao Huang Yu Guo Linxi Chen Jian Li |
| |
Institution: | (1) Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang, 421001, People’s Republic of China;(2) Department of Physiology, Hunan College of Traditional Chinese Medicine, Changsha, 410007, People’s Republic of China;(3) The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, 100730, People’s Republic of China; |
| |
Abstract: | Apelin is the endogenous ligand of the G-protein-coupled receptor, apelin–angiotensin receptor-like 1 (APJ). Vascular smooth
muscle cells express both apelin and APJ, which are important regulatory factors in the cardiovascular system. Apelin-13 significantly
stimulated vascular smooth muscle cell proliferation. However, little is known about the precise cellular mechanisms responsible
for vascular smooth muscle cell proliferation induced by apelin-13. Here, we present novel data that indicate the key role
of NADPH oxidase 4-derived reactive oxygen species in proliferation of vascular smooth muscle cells treated with apelin-13.
Apelin-13 stimulated reactive oxygen species production in a concentration- and time-dependent manner. Furthermore, DPI impaired
apelin-13-induced reactive oxygen species generation and vascular smooth muscle cell proliferation. Apelin-13-treatment increased
the expression of NADPH oxidase 4 in a dose-dependent manner. Down-regulation of NADPH oxidase 4 using siRNA prevented apelin-13-induced
reactive oxygen species generation and vascular smooth muscle cell proliferation. An increase in reactive molecules can trigger
the activation of ERK stress-sensitive signaling pathways. Additionally, siRNA-NOX4 and DPI reversed the phosphorylation of
ERK induced by apelin-13. Apelin-13 induced vascular smooth muscle cell proliferation by NOX4-derived ROS via the ERK signaling
pathway. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|