Type VIII Collagen Stimulates Smooth Muscle Cell Migration and Matrix Metalloproteinase Synthesis after Arterial Injury

Abstract

Type VIII collagen is a matrix protein expressed in a number of tissues undergoing active remodeling, including injured arteries during neointimal formation and in human atherosclerotic plaques; however, very little is known about its function. We have investigated whether the type VIII collagen stimulates smooth muscle cell (SMC) migration and invasion by binding to integrin receptors and up-regulating matrix metalloproteinase (MMP) production. SMCs attached to plates coated with type VIII collagen in a dose-dependent manner, with maximal attachment occurring with coating solutions containing 25 microgram/ml collagen. Type VIII collagen at 100 microgram/ml stimulated an 83-fold increase in the migration of SMCs in a chemotaxis chamber. Antibodies against beta1 integrin receptors prevented attachment and migration of SMCs. Antibodies against alpha1 or alpha2 integrins reduced attachment of SMCs to type VIII collagen by 29% and 77%, respectively. We found that SMCs grown from the rat neointima, but not medial SMCs, increased their production of MMP-2 and -9 on adherence to type VIII collagen. This suggests that there is an important difference in phenotype between intimal and medial SMCs and that intimal SMCs have distinct matrix-dependent signaling mechanisms. Our findings suggest that type VIII collagen deposited in vascular lesions functions to promote SMC attachment and chemotaxis, and signals through integrin receptors to stimulate MMP synthesis, all of which are important mechanisms used in cell migration and invasion.

Different Involvement of Extracellular Matrix Components in Small and Large Arteries During Chronic NO Synthase Inhibition

“…In 4 rats per group, MMP-2 activity was also measured by standard gelatin zymography 22 to confirm the results obtained with the commercial assay. MMP-2 was localized at 72 kDa, and its activity was visualized as areas of lytic activity on an otherwise blue background.…”

siRNA‐targeted COL8A1 inhibits proliferation, reduces invasion and enhances sensitivity to D‐limonence treatment in hepatocarcinoma cells

“…Pericellular COL8A1 may therefore function during development to help maintain cells in a proliferative state. COL8A1 has also been suggested to act as a chemotactic factor for mesenchymal cells such as smooth muscle cells and to provide a substrate for enhanced migration (8,18). The expression profile of COL8A1 gene may segregate gastrointestinal stromal tumors into groups of different tumor behavior (4).…”

“…Although the function of type VIII collagen is not known, its close association with endothelial cells has led to its proposed role in determining cell phenotype (6). Increasing evidence indicates that collagen type VIII plays a role in atherogenesis and vascular remodeling, presumably through modification of cell migration and proliferation (7,8). The short-chain type VIII collagen, thought to play a key role in angiogenesis, has been detected throughout the developmental phases of hemangioma (9).…”

Rear Polarization of the Microtubule-Organizing Center in Neointimal Smooth Muscle Cells Depends on PKCα, ARPC5, and RHAMM

“…15 Uninjured carotid arteries were harvested and stripped of adventitia, and the endothelium was scraped off; medial SMCs were then dispersed by digestion for 1 hour in 0.3 mg/ml elastase type III, 1.8 mg/ml collagenase type I (Worthington Biochemical, Freehold, NJ), 0.44 mg/ml soybean trypsin inhibitor, and 2 mg/ml bovine serum albumin. To obtain neointimal SMCs, left carotid arteries of rats were injured with a balloon catheter; 2 weeks later, the thickened neointima was stripped from the vessel with the aid of a dissecting microscope.…”