This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 46/3/614    most recent 01.HYP.0000175811.79863.e2v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shyu, K.-G. Articles by Kuan, P. Search for Related Content PubMed PubMed Citation Articles by Shyu, K.-G. Articles by Kuan, P. Related Collections Other Vascular biology Cell signalling/signal transduction Gene expression

(Hypertension. 2005;46:614.)
© 2005 American Heart Association, Inc.

Original Articles

Regulation of Discoidin Domain Receptor 2 by Cyclic Mechanical Stretch in Cultured Rat Vascular Smooth Muscle Cells

From the Department of Education and Research (K.G.S., B.W.W.) and Department of Internal Medicine (Y.M.C., P.K.), Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Graduate Institute of Medical Sciences (K.G.S.), College of Medicine, Taipei Medical University, Taiwan; and School of Medicine (K.G.S.), Fu-Jen Catholic University, Taipei, Taiwan.

Correspondence to Kou-Gi Shyu, Department of Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen-Chang Rd, Taipei, Taiwan. E-mail shyukg{at}ms12.hinet.net

Discoidin domain receptor 2 (DDR2) plays potential roles in the regulation of collagen turnover mediated by smooth muscle cells in atherosclerosis. How mechanical stretch affects the regulation of DDR2 in smooth muscle cells is not fully understood. We sought to investigate the cellular and molecular mechanisms of regulation of DDR2 by cyclic stretch in smooth muscle cells. Rat vascular smooth muscle cells grown on a flexible membrane base were stretched by vacuum to 20% of maximum elongation, at 60 cycles/min. Cyclic stretch significantly increased DDR2 protein and mRNA expression after stretch. Cyclic stretch also significantly increased DNA–protein binding activity of Myc-Max. Addition of SB203580, transforming growth factor-ß1 (TGF-ß1) monoclonal antibody, p38 small interfering RNA (siRNA), and c-myc siRNA 30 minutes before stretch inhibited the induction of DDR2 protein and abolished the DNA–protein binding activity induced by cyclic stretch. Cyclic stretch increased, whereas SB203580 abolished the phosphorylated p38 protein. Conditioned medium from stretched smooth muscle cells and exogenous administration of angiotensin II and TGF-ß1 recombinant proteins to the nonstretched cells increased DDR2 protein expression similar to that seen after stretch. In conclusion, cyclic mechanical stretch enhances DDR2 expression in cultured rat smooth muscle cells. The stretch-induced DDR2 is mediated by angiotensin II and TGF-ß1, at least in part, through p38 mitogen-activated protein kinase and Myc pathway.

Key Words: muscle, smooth, vascular • protein kinases • angiotensin II • transforming growth factors

This article has been cited by other articles:

				K.-G. Shyu, B.-W. Wang, P. Kuan, and H. Chang RNA Interference for Discoidin Domain Receptor 2 Attenuates Neointimal Formation in Balloon Injured Rat Carotid Artery Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1447 - 1453. [Abstract] [Full Text] [PDF]

				W.-P. Cheng, H.-F. Hung, B.-W. Wang, and K.-G. Shyu The molecular regulation of GADD153 in apoptosis of cultured vascular smooth muscle cells by cyclic mechanical stretch Cardiovasc Res, February 1, 2008; 77(3): 551 - 559. [Abstract] [Full Text] [PDF]

				G. Rajashekhar, M. Grow, A. Willuweit, C. E. Patterson, and M. Clauss Divergent and convergent effects on gene expression and function in acute versus chronic endothelial activation Physiol Genomics, September 11, 2007; 31(1): 104 - 113. [Abstract] [Full Text] [PDF]

				D. Tang, Y. Shi, R. Kang, T. Li, W. Xiao, H. Wang, and X. Xiao Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1 J. Leukoc. Biol., March 1, 2007; 81(3): 741 - 747. [Abstract] [Full Text] [PDF]