1. The present study was carried out to determine how levels of the mRNA of metalloproteinases (metalloproteinase-1, 72 kDa type IV collagenase, metalloproteinase-3 and 92 kDa type IV collagenase) and tissue inhibitor of metalloproteinases are regulated in the renal tissues of New Zealand Black/White F1 mice.
2. mRNA levels for metalloproteinase-1, 72 kDa type IV collagenase, metalloproteinase-3 and tissue inhibitor of metalloproteinases increased significantly with the progression of nephritis in New Zealand Black/White F1 mice.
3. At 48 weeks of age, the levels of mRNA for metalloproteinase-1, 72 kDa type IV collagenase, metalloproteinase-3 and tissue inhibitor of metalloproteinases increased by 8-, 4-, 8- and 15-fold, respectively, in the renal tissues of New Zealand Black/White F1 mice compared with New Zealand White mice.
4. In the kidneys of New Zealand White mice, however, the mRNA levels for these proteins changed little throughout the experimental period.
5. We could not detect expression of mRNA for 9 2 kDa type IV collagenase in the renal tissue of New Zealand Black/White F1 mice at 8 weeks of age or in New Zealand White mice at 8, 24 or 48 weeks of age, whereas we could detect expression of mRNA for this protein in New Zealand Black/White F1 mice at 24 and 48 weeks of age when mononuclear cells had infiltrated the interstitium and surrounding blood vessels.
6. At 24 weeks of age, New Zealand Black/White F1 mice were divided into two groups and received either methylprednisolone or saline injection for 24 weeks.
7. The development of histopathological lesions and increases in mRNA for metalloproteinases and tissue inhibitor of metalloproteinases were suppressed by treatment with methylprednisolone.
8. These data suggest that abnormal regulation of the genes for metalloproteinases and tissue inhibitor of metalloproteinases contribute to the accumulation of extracellular matrix components in lupus nephritis and that the beneficial effect of methylprednisolone is associated with its ability to suppress the expression of mRNA for metalloproteinases and tissue inhibitor of metalloproteinases.
Interaction of 92-kDa type IV collagenase with the tissue inhibitor of metalloproteinases prevents dimerization, complex formation with interstitial collagenase, and activation of the proenzyme with stromelysin.