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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 and Integrative Physiological Science, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115
Corresponding author. Department of Medical Engineering, Afeka Tel Aviv Academic College of Engineering, 218 Bney Efraim Rd. Tel Aviv 69107, Israel, 972-3-7688733 (phone), 972-3-7688691 (fax), RatnovskyA@afeka.ac.il
Division of Physiology, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205

Molecular & Cellular Biomechanics 2007, 4(3), 143-158. https://doi.org/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 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.

Keywords

obesity, airway smooth muscle, cytoskeleton remodeling, contractility, proliferation

Cite This Article

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. Molecular & Cellular Biomechanics, 4(3), 143–158.



This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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