Airway Smooth Muscle Proliferation and Mechanics: Effects of AMP Kinase Agonists
Anat Ratnovsky∗,†, Matthew Mellema*, Steven S. An∗,‡, Jeffrey J. Fredberg*, Stephanie A. Shore*
Molecular & Cellular Biomechanics, Vol.4, No.3, pp. 143-158, 2007, DOI:10.3970/mcb.2007.004.143
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-ß-D-riboruranoside (AICAR), also inhibited PDGF-induced proliferation. Furthermore, cells More >
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