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

Yang Song, Yuanyuan Wu, Xiaofan Su, Yanting Zhu, Lu Liu, Yilin Pan, Bo Zhu, Lan Yang, Li Gao, Manxiang Li

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)117-124
Number of pages8
JournalPharmacological Research
Volume107
DOIs
StatePublished - May 1 2016

Keywords

  • AMPK
  • Pulmonary arterial smooth muscle cells
  • Skp2
  • mTOR
  • p27

ASJC Scopus subject areas

  • Pharmacology

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