The complete primary structure of human matrix metalloproteinase-3. Identity with stromelysin

We have determined the complete primary structure for human matrix metalloproteinase-3 (MMP-3), which has 477 residues including a 17-residue signal peptide. The result indicates that MMP-3 is identical with stromelysin (Whitham, S. E., Murphy, G., Angel, P., Rahmsdorf, H.-J., Smith, B. J., Lyons, A., Harris, T. J. R., Reynolds, J. J., Herrlich, P., and Docherty, A. J. P. (1986) Biochem. J. 240, 913-916). A striking result is that MMP-3 and collagenase are 54% identical in sequence, suggesting a common origin for the evolution of the two proteinases. We also show that in human synovial fibroblast cultures human recombinant interleukin-1 beta rapidly induces high levels of MMP-3 mRNA and, conversely, that retinoic acid or dexamethasone can suppress the MMP-3 mRNA levels. Similar results were obtained for human synovial collagenase mRNA. The data suggest that MMP-3 and collagenase expression are coordinately modulated in synovial fibroblast cultures.