The discoidin domain receptor tyrosine kinase DDR1 in arterial wound repair

Collagens act as important signaling molecules regulating vascular smooth m uscle cell responses during arterial wound repair. Discoidin domain recepto rs (DDRs) are a never class of receptor tyrosine kinases that bind to sever al collagens and stimulate matrix metalloproteinase (MMP) production, but l ittle is known about their expression and function in the vasculature. We p osited a critical role for the DDRs controlling smooth muscle cell migratio n and proliferation and thus repair following arterial injury. Smooth muscl e cells were isolated from the aortas of mice with a targeted deletion of t he DDR1 gene (DDR1-null) and studied in culture using models that mimic cri tical steps in neointimal thickening. Our studies suggest that DDR1 plays a n important role in regulating attachment to collagen, chemotaxis, prolifer ation, and MMP production in smooth muscle cells. Following mechanical inju ry to the carotid arteries, cross-sectional area of the neointima was signi ficantly lower in DDR1-null mice than in wild-type mice. There was also a s ignificant decrease in collagen deposition in the injured arteries of the D DR1-null mice. Our results support the hypothesis that DDR1 plays an import ant role as a collagen receptor, mediating intimal thickening after vascula r injury.