Activation of AMPK inhibits PDGF-induced pulmonary arterial smooth muscle cells proliferation and its potential mechanisms

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• 作者：Yang Song^a ; ¹ ; Yuanyuan Wu^a ; ¹ ; Xiaofan Su^a ; Yanting Zhu^a ; Lu Liu^a ; Yilin Pan^a ; Bo Zhu^a ; Lan Yang^a ; Li Gao^b ; Manxiang Li^a ; ^{manxiangli@hotmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Pulmonary arterial smooth muscle cells ; AMPK ; mTOR ; p27 ; Skp2
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：107
• 期：Complete
• 页码：117-124
• 全文大小：1481 K

文摘

The aims of the present study were to examine signaling mechanisms for PDGF-induced pulmonary arterial smooth muscle cells (PASMC) proliferation and to determine the effect of AMPK activation on PDGF-induced PASMC proliferation and its underlying mechanisms. PDGF activated PI3K/Akt/mTOR signaling pathway, and this in turn up-regulated Skp2 and consequently reduced p27 leading to PASMC proliferation. Prior incubation of PASMC with metformin induced a dramatic AMPK activation and significantly blocked PDGF-induced cell proliferation. PASMC lacking AMPKα2 were resistant to the inhibitory effect of metformin on PDGF-induced cell proliferation. Metformin did not affect Akt activation but blocked mTOR phosphorylation in response to PDGF; these were accompanied by the reversion of Skp2 up-regulation and p27 reduction. Our study suggests that the activation of AMPK negatively regulates mTOR activity to suppress PASMC proliferation and therefore has a potential value in the prevention and treatment of pulmonary hypertension by negatively modulating pulmonary vascular remodeling.