Knockdown of AMPKα2 promotes pulmonary arterial smooth muscle cells proliferation via mTOR/Skp2/p27Kip1 signaling pathway

Rui Ke, Lu Liu, Yanting Zhu, Shaojun Li, Xinming Xie, Fangwei Li, Yang Song, Lan Yang, Li Gao, Manxiang Li

Research output: Contribution to journalArticle

Abstract

It has been shown that activation of adenosine monophosphate-activated protein kinase (AMPK) suppresses proliferation of a variety of tumor cells as well as nonmalignant cells. In this study, we used post-transcriptional gene silencing with small interfering RNA (siRNA) to specifically examine the effect of AMPK on pulmonary arterial smooth muscle cells (PASMCs) proliferation and to further elucidate its underlying molecular mechanisms. Our results showed that knockdown of AMPKα2 promoted primary cultured PASMCs proliferation; this was accompanied with the elevation of phosphorylation of mammalian target of rapamycin (mTOR) and S-phase kinase-associated protein 2 (Skp2) protein level and reduction of p27Kip1. Importantly, prior silencing of mTOR with siRNA abolished AMPKα2 knockdown-induced Skp2 upregulation, p27Kip1 reduction as well as PASMCs proliferation. Furthermore, pre-depletion of Skp2 by siRNA also eliminated p27Kip1 downregulation and PASMCs proliferation caused by AMPKα2 knockdown. Taken together, our study indicates that AMPKα2 isoform plays an important role in regulation of PASMCs proliferation by modulating mTOR/Skp2/p27Kip1 axis, and suggests that activation of AMPKα2 might have potential value in the prevention and treatment of pulmonary arterial hypertension.

Original languageEnglish (US)
Article number844
JournalInternational journal of molecular sciences
Volume17
Issue number6
DOIs
StatePublished - Jun 1 2016

Keywords

  • AMPK
  • MTOR
  • Proliferation
  • Pulmonary arterial smooth muscle cells
  • Skp2

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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