Apelin inhibits the proliferation and migration of rat PASMCs via the activation of PI3K/Akt/mTOR signal and the inhibition of autophagy under hypoxia

Journal of Cellular and Molecular Medicine

Hongyu Zhang¹  Yongsheng Gong²  Zhouguang Wang¹  Liping Jiang³  Ran Chen²  Xiaofang Fan²  Huanmian Zhu²  Liping Han²  Xiaokun Li¹  Jian Xiao¹ 

[1] School of Pharmacy, Zhejiang Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, China;School of Basic Medical Sciences, Institute of Hypoxia Research, Wenzhou Medical University, Wenzhou, Zhejiang, China;School of Nursing, Wenzhou Medical University, Wenzhou, Zhejiang, China

关键词: apelin;    hypoxia;    autophagy;    PI3K/Akt/mTOR;    smooth muscle cells;   

DOI  :  10.1111/jcmm.12208

来源: Wiley

【 摘 要 】

Abstract

Apelin is highly expressed in the lungs, especially in the pulmonary vasculature, but the functional role of apelin under pathological conditions is still undefined. Hypoxic pulmonary hypertension is the most common cause of acute right heart failure, which may involve the remodeling of artery and regulation of autophagy. In this study, we determined whether treatment with apelin regulated the proliferation and migration of rat pulmonary arterial smooth muscle cells (SMCs) under hypoxia, and investigated the underlying mechanism and the relationship with autophagy. Our data showed that hypoxia activated autophagy significantly at 24 hrs. The addition of exogenous apelin decreased the level of autophagy and further inhibited pulmonary arterial SMC (PASMC) proliferation via activating downstream phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/the mammalian target of Rapamycin (mTOR) signal pathways. The inhibition of the apelin receptor (APJ) system by siRNA abolished the inhibitory effect of apelin in PASMCs under hypoxia. This study provides the evidence that exogenous apelin treatment contributes to inhibit the proliferation and migration of PASMCs by regulating the level of autophagy.

【 授权许可】

CC BY   
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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