Participation of the matrix metalloproteinase inhibitor in Thy-1 nephritis.
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.
Mitani
Osamu
O
Department of Pathology, Shinshu University School of Medicine, Matsumoto, Japan. osamu_mitani@maruishi-pharm.co.jp
Katoh
Masahiro
M
Shigematsu
Hidekazu
H
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D024042:Collagen Type I / Q000187:drug effects / Q000378:metabolism; D024141:Collagen Type IV / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000473:pathology*; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018800:Thy-1 Antigens / Q000276:immunology
D000199:Actins; D024042:Collagen Type I; D024141:Collagen Type IV; D004791:Enzyme Inhibitors; D009842:Oligopeptides; C421267:SI 27; D018800:Thy-1 Antigens; D020782:Matrix Metalloproteinases