Tyrosine Kinase Activity of Discoidin Domain Receptor 1 Is Necessary for Smooth Muscle Cell Migration and Matrix Metalloproteinase Expression

• Published in: Circulation research Vol. 90; no. 11; pp. 1147 - 1149
• Main Authors: Hou, Guangpei, Vogel, Wolfgang F, Bendeck, Michelle P
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 14.06.2002; Lippincott; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Animals; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Adhesion - physiology; Cell Movement - physiology; Discoidin Domain Receptors; Genotype; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinases - biosynthesis; Medical sciences; Mice; Mice, Inbred Strains; Mice, Knockout; Microscopy, Confocal; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - metabolism; Protein-Tyrosine Kinases - metabolism; Receptor Protein-Tyrosine Kinases; Receptors, Mitogen - genetics; Receptors, Mitogen - metabolism; Transfection; Pathogenesis; Migration; Cardiovascular disease; Metalloendopeptidases; Smooth muscle; Vascular disease; Enzymatic activity; Blood vessel; Atherosclerosis; Aorta; Protein-tyrosine kinase; Biological receptor; Enzyme; Transferases; Rodentia; Gene expression; Artery; Restenosis; Peptidases; Vertebrata; Mammalia; Mouse; Animal; Collagen; Hydrolases; Circulatory system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.0000022166.74073.f8

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.