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Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation

Cited 26 time in Web of Science Cited 28 time in Scopus
Authors

Karki, Rajendra; Kim, Seong-Bin; Kim, Dong-Wook

Issue Date
2013-12
Publisher
Academic Press
Citation
Experimental Cell Research, Vol.319 No.20, pp.3238-3250
Abstract
Background: Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. Methods: The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-alpha) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of beta 1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. Results: VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited beta 1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited beta 1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Conclusions: Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. General significance: This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.
ISSN
0014-4827
URI
https://hdl.handle.net/10371/203066
DOI
https://doi.org/10.1016/j.yexcr.2013.07.016
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  • College of Natural Sciences
  • School of Biological Sciences
Research Area Cytokine Storm, Host Defense, Innate Immunity in Metabolic and Inflammatory Diseases

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