The discoidin domain receptor tyrosine kinase DDR1 in arterial wound repair
Guangpei Hou, Wolfgang Vogel, Michelle P. Bendeck
Guangpei Hou, Wolfgang Vogel, Michelle P. Bendeck
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The discoidin domain receptor tyrosine kinase DDR1 in arterial wound repair

Abstract

Collagens act as important signaling molecules regulating vascular smooth muscle cell responses during arterial wound repair. Discoidin domain receptors (DDRs) are a novel class of receptor tyrosine kinases that bind to several collagens and stimulate matrix metalloproteinase (MMP) production, but little is known about their expression and function in the vasculature. We posited a critical role for the DDRs controlling smooth muscle cell migration and proliferation and thus repair following arterial injury. Smooth muscle cells were isolated from the aortas of mice with a targeted deletion of the DDR1 gene (DDR1-null) and studied in culture using models that mimic critical steps in neointimal thickening. Our studies suggest that DDR1 plays an important role in regulating attachment to collagen, chemotaxis, proliferation, and MMP production in smooth muscle cells. Following mechanical injury to the carotid arteries, cross-sectional area of the neointima was significantly lower in DDR1-null mice than in wild-type mice. There was also a significant decrease in collagen deposition in the injured arteries of the DDR1-null mice. Our results support the hypothesis that DDR1 plays an important role as a collagen receptor, mediating intimal thickening after vascular injury.

Authors

Guangpei Hou, Wolfgang Vogel, Michelle P. Bendeck

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SMC attachment to collagen was reduced in the absence of DDR1. SMCs from...
SMC attachment to collagen was reduced in the absence of DDR1. SMCs from DDR1+/+ mice (filled bars) or DDR1–/– mice (open bars) were allowed to attach for 4 hours to plates coated with 10 nM fibronectin or vitronectin or 100 nM type I collagen or type VIII collagen. Attachment was assessed by staining the cells with toluidine blue and measuring optical density at 595 nm. Experiments were done in triplicate and repeated three times. AValue from DDR1–/– SMCs was significantly less than the value from wild-type SMCs.