Participation of the matrix metalloproteinase inhibitor in Thy-1 nephritis.

ABSTRACT

What influence would be shown in Thy-1 glomerulonephritis when the synthetic matrix metalloproteinase (MMP) inhibitor SI-27 is administered? Five groups of 80 male Wistar rats were studied healthy group; treated healthy group; nephritic group; pretreated nephritic group; and post-treated nephritic group. SI-27 treatment of nephritic animals was initiated either 2 days before or 2 days after anti-Thy-1.1 antibody injection. On days 7, 14, 26 and 42 after disease induction, we examined renal histology, extracellular matrix (ECM) constituent, and MMP activity. SI-27 treated Thy-1 groups resulted in significant reduction of glomerular cells including alpha-smooth muscle actin (alpha-SMA) positive mesangial cells and suppressed expression of type IV collagen at 7 days. Moreover, type I collagen was also decreased by SI-27 at 42 days. However, glomerular cell numbers did not show any significant changes at 14, 26 and 42 days. In gelatin zymography, the gelatinolytic band for MMP-9 was expressed in SI-27 treated Thy-1 nephritis groups, although it was not expressed in the nephritic group at day 7. However, the expression of MMP-9 was no longer seen at 14, 26 and 42 days. The bands for an active form of MMP-2 were expressed throughout the experimental period in the Thy-1 nephritic groups. These results suggest that MMP plays an important role in the development of Thy-1 nephritis, and even if the synthetic MMP inhibitor intercepts the initial increase of glomerular cells and matrices, it does not inhibit recovery to normal glomerular capillary structures in Thy-1 nephritis.