Metformin inhibits inflammatory response via AMPK-PTEN pathway in vascular smooth muscle cells

Title
Metformin inhibits inflammatory response via AMPK-PTEN pathway in vascular smooth muscle cells
Author(s)
최형철김선애
Keywords
ACTIVATED PROTEIN-KINASE; PROSTATE-CANCER CELLS; 5-AMINOIMIDAZOLE-4-CARBOXAMIDE RIBOSIDE; PROINFLAMMATORY RESPONSES; NEOINTIMA FORMATION; DOWN-REGULATION; KAPPA-B; EXPRESSION; ATHEROSCLEROSIS; PROLIFERATION
Issue Date
201209
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.425, no.4, pp.866 - 872
Abstract
Atherosclerosis is a chronic inflammation of the coronary arteries. Vascular smooth muscle cells (VSMCs) stimulated by cytokines and chemokines accelerate the inflammatory response and migrate to the injured endothelium during the progression of atherosclerosis. Activation of AMP activated protein kinase (AMPK), a key sensor maintaining metabolic homeostasis, suppresses the inflammatory response. However, how AMPK regulates the inflammatory response is poorly understood. To identify the mechanism of this response, we focused on phosphatase and tensin homolog (PTEN), which is a negative regulator of inflammation. We investigated that activation of AMPK-induced PTEN expression and suppression of the inflammatory response through the AMPK-PTEN pathway in VSMCs. We treated with the well-known AMPK activator metformin to induce PTEN expression. PTEN was induced by metformin (2 mM) and inhibited by compound C (10 mu M) and AMPK siRNA. Tumor necrosis factor-alpha (TNE-alpha) was used to induce inflammation. The inflammatory response was confirmed by cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expression, and activation of nuclear factor (NF)-kappa B. Metformin suppressed COX-2 and iNOS mRNA and protein expression dose dependently. Treatment with compound C and bpv (pic) in the presence of metformin, iNOS and COX-2 protein expression increased. NF-kappa B activation decreased in response to metformin and was restored by inhibiting AMPK and PTEN. Inhibiting AMPK and PTEN restored ROS levels stimulated with INF-alpha. Taken together, PTEN could be a possible downstream regulator of AMPK, and the AMPK-PTEN pathway might be important in the regulation of the inflammatory response in VSMCs. (C) 2012 Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/27340http://dx.doi.org/10.1016/j.bbrc.2012.07.165
ISSN
0006-291X
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의과대학 > 약리학교실 > Articles
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