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Activation of AMPK α2 inhibits airway smooth muscle cells proliferation

Lu Liu1, Yilin Pan1, Yang Song1

  • 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.

European Journal of Pharmacology
|September 8, 2016
PubMed

Insights

Adenosine monophosphate-activated protein kinase (AMPK) activation inhibits airway smooth muscle cell proliferation by suppressing mTOR signaling. This finding suggests AMPK as a potential therapeutic target for asthma and airway remodeling.

Area of Science:

  • Cell Biology
  • Pharmacology
  • Respiratory Medicine

Background:

  • Airway smooth muscle cell (ASMC) proliferation contributes to airway remodeling in asthma.
  • Platelet-derived growth factor (PDGF) signaling promotes ASMC proliferation via the PI3K/Akt/mTOR pathway.
  • Understanding regulators of ASMC proliferation is crucial for asthma treatment.

Purpose of the Study:

  • To investigate the effect of adenosine monophosphate-activated protein kinase (AMPK) activation on ASMC proliferation.
  • To elucidate the underlying molecular mechanisms of AMPK's action on ASMCs.
  • To assess the therapeutic potential of AMPK activation in airway remodeling.

Main Methods:

  • ASMCs were treated with PDGF and metformin (an AMPK activator).
  • Western blotting was used to analyze protein expression (p-mTOR, Skp2, p27, p-Akt).
  • AMPK α2-specific small interfering RNA (siRNA) was employed to confirm AMPK's role.

Main Results:

  • PDGF induced ASMC proliferation by activating the PI3K/Akt/mTOR pathway, upregulating Skp2, and downregulating p27.
  • Metformin inhibited PDGF-induced mTOR activation, altered Skp2 and p27 levels, and suppressed ASMC proliferation.
  • AMPK α2-siRNA transfection reversed the inhibitory effects of metformin, confirming AMPK α2's critical role.

Conclusions:

  • AMPK activation, particularly via AMPK α2, negatively regulates mTOR signaling to inhibit ASMC proliferation.
  • AMPK activation suppresses key mediators of cell cycle progression (Skp2 and p27).
  • AMPK activation holds potential for preventing and treating asthma by modulating airway remodeling.
Keywords:
AMPKAirway smooth muscle cellsLY294002 (PubChem CID: 11957589)MTORP27Rapamycin (PubChem CID: 5284616)Skp2

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