Elevated expression of membrane-type 1 and 3 matrix metalloproteinases in rat vascular smooth muscle cells activated by arterial injury.

Matrix metalloproteinases (MMPs) play critical roles in tissue remodeling under various physiologic and pathologic conditions. We recently reported the expression of three membrane-type MMPs (MT-MMPs) by cultured vascular smooth muscle cells (SMCs) of rats (Shofuda et al, 1997). To investigate the roles of the MT-MMPs in the matrix remodeling of blood vessels, expression of MT1-MMP and MT3-MMP was examined in normal and balloon-injured rat carotid arteries by in situ hybridization and immunohistochemistry. Both MT-MMP mRNAs were detected in the intimal-dedifferentiated SMCs, but were negligible in the medial SMCs or in any of normal vascular cells. To elucidate the regulatory mechanism for the MT-MMPs expression, effects of various factors on cultured rat SMCs were also examined. MT1-MMP mRNA was constantly expressed at a high level, and its expression was weakly increased by treatment with interleukin-1beta or tumor necrosis factor-alpha. When the cells were incubated with type IV collagen, the MT1 -MMP expression was markedly decreased. On the other hand, expression of MT3-MMP mRNA was strongly increased by platelet-derived growth factor and fibronectin. These results suggest that type IV collagen may act as a negative regulator for the expression of MT1-MMP in the medial SMCs, whereas platelet-derived growth factor and fibronectin may up-regulate MT3-MMP expression under pathologic conditions. Furthermore, the elevated expression of MT1-MMP and MT3-MMP in SMCs was well associated with their dedifferentiated phenotype.