Knockdown of AMPKα2 Promotes Pulmonary Arterial Smooth Muscle Cells Proliferation via mTOR/Skp2/p27(Kip1) 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 p27(Kip1). Importantly, prior silencing of mTOR with siRNA abolished AMPKα2 knockdown-induced Skp2 upregulation, p27(Kip1) reduction as well as PASMCs proliferation. Furthermore, pre-depletion of Skp2 by siRNA also eliminated p27(Kip1) 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/p27(Kip1) axis, and suggests that activation of AMPKα2 might have potential value in the prevention and treatment of pulmonary arterial hypertension.

Original languageEnglish (US)
JournalInternational Journal of Molecular Sciences
Volume17
Issue number6
DOIs
StatePublished - May 31 2016

Fingerprint

S-Phase Kinase-Associated Proteins
smooth muscle
muscle cells
Cell proliferation
Sirolimus
Smooth Muscle Myocytes
Muscle
Cell Proliferation
proteins
Proteins
Lung
Small Interfering RNA
RNA
Adenosine Monophosphate
adenosine monophosphate
Protein Kinases
Chemical activation
Phosphorylation
RNA Interference
activation

Keywords

  • AMPK
  • mTOR
  • proliferation
  • pulmonary arterial smooth muscle cells
  • Skp2

ASJC Scopus subject areas

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

Cite this

Knockdown of AMPKα2 Promotes Pulmonary Arterial Smooth Muscle Cells Proliferation via mTOR/Skp2/p27(Kip1) Signaling Pathway. / Ke, Rui; Liu, Lu; Zhu, Yanting; Li, Shaojun; Xie, Xinming; Li, Fangwei; Song, Yang; Yang, Lan; Gao, Li; Li, Manxiang.

In: International Journal of Molecular Sciences, Vol. 17, No. 6, 31.05.2016.

Research output: Contribution to journalArticle

Ke, Rui ; Liu, Lu ; Zhu, Yanting ; Li, Shaojun ; Xie, Xinming ; Li, Fangwei ; Song, Yang ; Yang, Lan ; Gao, Li ; Li, Manxiang. / Knockdown of AMPKα2 Promotes Pulmonary Arterial Smooth Muscle Cells Proliferation via mTOR/Skp2/p27(Kip1) Signaling Pathway. In: International Journal of Molecular Sciences. 2016 ; Vol. 17, No. 6.
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