Airway smooth muscle proliferation and mechanics: Effects of AMP kinase agonists

Anat Ratnovsky, Matthew Mellema, Steven S. An, Jeffrey J. Fredberg, Stephanie A. Shore

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Obesity is a risk factor for asthma. The purpose of this study was to determine whether metformin, an agent used in the treatment of an obesity-related condition (type II diabetes), might have therapeutic potential for modifying the effects of obesity on airway smooth muscle (ASM) function. Metformin acts via activation of AMP-activated protein kinase (AMPK), a cellular sensor of energy status. In cultured murine ASM cells, metformin (0.2-2 mM) caused a dose-dependent inhibition of cell proliferation induced by PDGF (10-8 M) and serotonin (10-4 M). Another AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-D-riboruranoside (AICAR), also inhibited PDGF-induced proliferation. Furthermore, cells treated with metformin or AICAR, also exhibited an attenuation in the rate of cytoskeletal remodeling, as quantified by spontaneous nanoscale motions of microbeads tightly anchored to the cytoskeleton (CSK) of the ASM cell. ASM cells treated with metformin or AICAR, however, exhibited no appreciable differences in stiffness as measured by optical magnetic twisting cytometry (OMTC) or their abilities to stiffen in response to contractile agonist serotonin. Taken together, these findings suggest that metformin, probably through activation of AMPK, reduces the rate of ongoing reorganization of the CSK and inhibits ASM cell proliferation.

Original languageEnglish (US)
Pages (from-to)143-157
Number of pages15
JournalMCB Molecular and Cellular Biomechanics
Volume4
Issue number3
StatePublished - Sep 2007
Externally publishedYes

Keywords

  • Airway smooth muscle
  • Contractility
  • Cytoskeleton remodeling
  • Obesity
  • Proliferation

ASJC Scopus subject areas

  • Cell Biology
  • Biophysics
  • Molecular Biology
  • Molecular Medicine

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  • Cite this

    Ratnovsky, A., Mellema, M., An, S. S., Fredberg, J. J., & Shore, S. A. (2007). Airway smooth muscle proliferation and mechanics: Effects of AMP kinase agonists. MCB Molecular and Cellular Biomechanics, 4(3), 143-157.