Open AccessApelin inhibits the proliferation and migration of rat PASMC s via the activation of PI3K/Akt/m TOR signal and the inhibition of autophagy under hypoxia
Author(s) -
Zhang Hongyu,
Gong Yongsheng,
Wang Zhouguang,
Jiang Liping,
Chen Ran,
Fan Xiaofang,
Zhu Huanmian,
Han Liping,
Li Xiaokun,
Xiao Jian,
Kong Xiaoxia
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12208
Subject(s) - apelin , autophagy , pi3k/akt/mtor pathway , protein kinase b , hypoxia (environmental) , microbiology and biotechnology , signal transduction , biology , chemistry , endocrinology , receptor , medicine , biochemistry , apoptosis , organic chemistry , oxygen
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 ( SMC s) 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 si RNA abolished the inhibitory effect of apelin in PASMC s under hypoxia. This study provides the evidence that exogenous apelin treatment contributes to inhibit the proliferation and migration of PASMC s by regulating the level of autophagy.