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
Published March 15, 2001
Citation Information: J Clin Invest. 2001;107(6):727-735. https://doi.org/10.1172/JCI10720.
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Article

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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Figure 1

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(a) DDR1 was activated by type I and type VIII collagen. HEK 293 cells w...
(a) DDR1 was activated by type I and type VIII collagen. HEK 293 cells were transfected with vector alone or DDR1 cDNA. The cells were incubated with plain media (C), 10 μg/ml type I collagen (I), or 10 μg/ml type VIII collagen (VIII) for 90 minutes, then cell lysates were collected and subjected to Western blotting. The same blots were sequentially probed with anti-phosphotyrosine (anti-P-Tyr) Ab (upper) and with DDR1 Ab (lower). (b) DDR1 mRNA expression was increased after injury of the rat carotid artery. Northern blot with RNA extracted from control carotids (C) and from carotids at various days after injury, then probed with a cDNA against mouse DDR1. Lower photograph is the methylene-blue–stained Northern blot showing 28s and 18s ribosomal RNA bands demonstrating equal loading in the lanes. (c) A Western blot, with arterial protein extracts from control carotids (C) and carotids taken at various times after injury, was probed with anti-human DDR1 Ab.