Hou G, Vogel W, Bendeck M P
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
J Clin Invest. 2001 Mar;107(6):727-35. doi: 10.1172/JCI10720.
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.
胶原蛋白作为重要的信号分子，在动脉创伤修复过程中调节血管平滑肌细胞反应。盘状结构域受体（DDRs）是一类新型的受体酪氨酸激酶，可与多种胶原蛋白结合并刺激基质金属蛋白酶（MMP）的产生，但对其在脉管系统中的表达和功能了解甚少。我们推测DDRs在控制平滑肌细胞迁移和增殖以及动脉损伤后的修复中起关键作用。从DDR1基因靶向缺失的小鼠（DDR1基因敲除小鼠）主动脉中分离出平滑肌细胞，并在培养中使用模拟内膜增厚关键步骤的模型进行研究。我们的研究表明，DDR1在调节平滑肌细胞与胶原蛋白的附着、趋化性、增殖和MMP产生中起重要作用。对颈动脉进行机械损伤后，DDR1基因敲除小鼠的新生内膜横截面积显著低于野生型小鼠。DDR1基因敲除小鼠损伤动脉中的胶原蛋白沉积也显著减少。我们的结果支持以下假设：DDR1作为胶原蛋白受体发挥重要作用，介导血管损伤后的内膜增厚。
