GENE-EXPRESSION OF METALLOPROTEINASES AND THEIR INHIBITOR IN RENAL TISSUE OF NEW-ZEALAND BLACK-WHITE F(1)-MICE

1. The present study was carried out to determine how levels of the mR NA of metalloproteinases (metalloproteinase-1, 72 kDa type IV collagen ase, metalloproteinase-3 and 92 kDa type IV collagenase) and tissue in hibitor of metalloproteinases are regulated in the renal tissues of Ne w 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, t he levels of mRNA for metalloproteinase-1, 72 kDa type IV collagenase, metalloproteinase-3 and tissue inhibitor of metalloproteinases increa sed by 8-, 4-, 8- and 15-fold, respectively, in the renal tissues of N ew Zealand Black/White F1 mice compared with New Zealand White mice. 4 . In the kidneys of New Zealand White mice, however, the mRNA levels f or these proteins changed little throughout the experimental period. 5 . We could not detect expression of mRNA for 9 2 kDa type IV collagena se in the renal tissue of New Zealand Black/White F1 mice at 8 weeks o f age or in New Zealand White mice at 8, 24 or 48 weeks of age, wherea s we could detect expression of mRNA for this protein in New Zealand B lack/White F1 mice at 24 and 48 weeks of age when mononuclear cells ha d infiltrated the interstitium and surrounding blood vessels. 6. At 24 weeks of age, New Zealand Black/White F1 mice were divided into two g roups and received either methylprednisolone or saline injection for 2 4 weeks.7. The development of histopathological lesions and increases in mRNA for metalloproteinases and tissue inhibitor of metalloproteina ses were suppressed by treatment with methylprednisolone. 8. These dat a suggest that abnormal regulation of the genes for metalloproteinases and tissue inhibitor of metalloproteinases contribute to the accumula tion of extracellular matrix components in lupus nephritis and that th e beneficial effect of methylprednisolone is associated with its abili ty to suppress the expression of mRNA for metalloproteinases and tissu e inhibitor of metalloproteinases.