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 inhibits the proliferation and migration of rat PASMCs via the activation of PI3K/Akt/mTOR signal and the inhibition of autophagy under hypoxia.
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Apelin通过激活PI3K/Akt/mTOR信号并抑制缺氧条件下自噬抑制大鼠PASMCs增殖和迁移

DOI:
10.1111/jcmm.12208
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发表时间:
2014-03
影响因子:
5.3
通讯作者:
Kong X
Kong X
中科院分区:
医学2区
文献类型:
--
作者:
Zhang H;Gong Y;Wang Z;Jiang L;Chen R;Fan X;Zhu H;Han L;Li X;Xiao J;Kong X

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爱帕琳在肺中高度表达,特别是在肺血管系统中,但爱帕琳在病理条件下的功能作用仍不明确。低氧性肺动脉高压是急性右心衰竭最常见的原因,其机制可能与动脉重构和自噬调节有关。在这项研究中,我们确定了apelin治疗是否调节大鼠肺动脉平滑肌细胞(SMCs)在缺氧条件下的增殖和迁移,并探讨了潜在的机制和自噬的关系。我们的数据表明,缺氧激活自噬在24小时显着。外源性apelin的加入降低了自噬水平,并通过激活下游磷脂酰肌醇-3-激酶(PI 3 K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路进一步抑制肺动脉SMC(PASMC)增殖。通过siRNA抑制apelin受体(APJ)系统,可消除apelin对缺氧PASMCs的抑制作用。本研究为外源性apelin通过调节自噬水平抑制PASMCs增殖和迁移提供了证据。
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.
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