These authors had equal contribution and are designated as co-first authors.
Apelin inhibits the proliferation and migration of rat PASMCs via the activation of PI3K/Akt/mTOR signal and the inhibition of autophagy under hypoxia
Article first published online: 22 JAN 2014
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Cellular and Molecular Medicine
Volume 18, Issue 3, pages 542–553, March 2014
How to Cite
Zhang, H., Gong, Y., Wang, Z., Jiang, L., Chen, R., Fan, X., Zhu, H., Han, L., Li, X., Xiao, J. and Kong, X. (2014), 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, 18: 542–553. doi: 10.1111/jcmm.12208
- Issue published online: 27 FEB 2014
- Article first published online: 22 JAN 2014
- Manuscript Accepted: 15 NOV 2013
- Manuscript Received: 30 AUG 2013
- National Natural Science Foundation of China. Grant Numbers: 81200010, 81200958, 81100138
- Zhejiang Natural Science Foundation. Grant Numbers: Y12H01003, Y2091033
- Protein Medicine Key Group. Grant Number: 2010R50042
- smooth muscle cells
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.