Tyrosine kinase activity of discoidin domain receptor 1 is necessary for smooth muscle cell migration and matrix metalloproteinase expression

被引:119
作者
Hou, GP [1 ]
Vogel, WF [1 ]
Bendeck, MP [1 ]
机构
[1] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada
关键词
matrix metalloproteinases; smooth muscle cell migration; discoidin domain receptors;
D O I
10.1161/01.RES.0000022166.74073.F8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Smooth muscle cell (SMC) interactions with collagen mediate cell migration during the pathogenesis of atherosclerosis and restenosis. Discoidin domain receptors (DDRs) have been identified as novel collagen receptors. We used aortic SMCs from wild-type and DDR1(-/-) mice to evaluate the function of the DDR1 in regulating migration. DDR1(-/-) SMCs exhibited impaired attachment to and migration toward a type I collagen substrate. Matrix metalloproteinase-2 (MMP-2) and MMP-9 activities were concomitantly reduced in these cells. Transfection of a full-length cDNA for DDR1b rescued these deficits, whereas kinase-dead mutants of DDR1 restored attachment but not migration and MMP production. These results suggest that active DDR1 kinase is a central mediator of SMC migration.
引用
收藏
页码:1147 / 1149
页数:3
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