Apelin inhibits the proliferation and migration of rat PASMCs via the activation of PI3K/Akt/mTOR signal and the inhibition of autophagy under hypoxia.
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.
School of Pharmacy, Zhejiang Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Hongyu
H
Zhang
Yongsheng
Y
Gong
Zhouguang
Z
Wang
Liping
L
Jiang
Ran
R
Chen
Xiaofang
X
Fan
Huanmian
H
Zhu
Liping
L
Han
Xiaokun
X
Li
Jian
J
Xiao
Xiaoxia
X
Kong
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D054392:Adipokines; D000818:Animals; D000073861:Apelin; D001343:Autophagy / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology; D034741:RNA, Small Interfering / Q000378:metabolism; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014162:Transfection
D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; C025946:3-methyladenine; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D000225:Adenine
PI3K/Akt/mTOR; apelin; autophagy; hypoxia; smooth muscle cells