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Papers In Press, published online ahead of print December 28, 2001
J. Biol. Chem, 10.1074/jbc.M111213200
Submitted on November 26, 2001
Revised on December 22, 2001
Accepted on December 28, 2001

Increased MMP-2 Expression in CTGF Over-expression vascular smooth muscle cells

Wen-Hua Fan and Morris J. Karnovsky

Pathology, Harvard Medical School, Boston, MA 02115

Corresponding Author: wenhua_fan{at}hms.harvard.edu

Connective tissue growth factor (CTGF) is abundantly expressed in the vascular smooth muscle cells (VSMC) of atherosclerotic lesions but not in normal vessels. CTGF is able to promote VSMC proliferation and migration and influences the composition of extracellular matrix (ECM). The mechanisms for controlling these events remain unclear. We studied the effects of CTGF on matrix metalloproteinases (MMPs) by introducing a CTGF over-expression construct into VSMC. We found that the over-expression of CTGF significantly increased the activity of MMP-2 in VSMC conditioned medium. The MMP-2 activity was similarly increased by exogenous CTGF treatment and this effect could be blocked by an anti-CTGF antibody. We also showed that the increased MMP-2 activity was due to an increase of MMP-2 mRNA levels in VSMC. We further studied the mechanisms involved in the regulation of MMP-2 mRNA levels and found that AP-2 transcription factor is responsible for most of the CTGF induced MMP-2 transcription. Since MMP-2 is an important factor directly involved in controlling cell movement and the turnover of ECM, our study may provide a mechanism for CTGF- promoted VSMC migration.


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