Resistin has a potential role in atherosclerosis; however, the molecular mechanism underlying the increase in resistin expression in atherosclerosis remains unclear. As mechanical stretch plays an important role in atherosclerosis, in the present study we sought to investigate the cellular and molecular mechanisms underlying the regulation of resistin by cyclic mechanical stretch in VSMCs (vascular smooth muscle cells). VSMCs from thoracic aorta of adult Wistar rats were cultured and subjected to cyclic stretch. Cyclic mechanical stretch significantly increased resistin protein and mRNA expression as compared with control cells without stretch. The specific p38 MAPK (mitogen-activated protein kinase) inhibitor SB203580, the antioxidant N-acetylcysteine and p38 MAPK siRNA (small interfering RNA) attenuated the induction of resistin protein by cyclic stretch. Cyclic stretch significantly increased the phosphorylation of p38 MAPK, whereas pre-treatment with SB203580 and N-acetylcysteine significantly inhibited this effect. Cyclic stretch significantly increased ROS (reactive oxygen species) production, and pre-treatment with N-acetylcysteine significantly inhibited stretch-induced ROS production. Cyclic stretch also increased STAT3 (signal transducer and activator of transcription 3)-binding activity and resistin promoter activity, and resistin promoter activity was abolished when STAT3 in the promoter area was mutated. Pre-treatment with SB203580 and N-acetylcysteine significantly attenuated resistin promoter activity induced by cyclic stretch. Cyclic stretch increased the secretion of AngII (angiotensin II) and resistin from cultured VSMCs. Exogenous AngII increased resistin expression, and AngII receptor inhibition attenuated this effect. In conclusion, cyclic mechanical stretch increases resistin expression in cultured rat VSMCs. Stretch-induced resistin expression is mediated through ROS, and the p38 MAPK and STAT3 pathways. Therefore resistin induced by cyclic stretch may contribute to the pathogenesis of atherosclerosis under haemodynamic overload.
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Research Article|
February 01 2010
Regulation of resistin by cyclic mechanical stretch in cultured rat vascular smooth muscle cells
Bao-Wei Wang;
Bao-Wei Wang
*School of Medicine, Fu-Jen Catholic University, Taipei County, Taiwan
†Department of Medical Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
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Hang Chang;
Hang Chang
†Department of Medical Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
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Kou-Gi Shyu
‡Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
§Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Correspondence: Professor Kou-Gi Shyu (email [email protected]).
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Publisher: Portland Press Ltd
Received:
March 17 2009
Revision Received:
June 16 2009
Accepted:
July 17 2009
Accepted Manuscript online:
July 17 2009
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2010 Biochemical Society
2010
Clin Sci (Lond) (2010) 118 (3): 221–230.
Article history
Received:
March 17 2009
Revision Received:
June 16 2009
Accepted:
July 17 2009
Accepted Manuscript online:
July 17 2009
Connected Content
A retraction has been published:
Retraction: Regulation of resistin by cyclic mechanical stretch in cultured rat vascular smooth muscle cells
Citation
Bao-Wei Wang, Hang Chang, Kou-Gi Shyu; Regulation of resistin by cyclic mechanical stretch in cultured rat vascular smooth muscle cells. Clin Sci (Lond) 1 February 2010; 118 (3): 221–230. doi: https://doi.org/10.1042/CS20090155
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