Participation of macrophages in glomerular sclerosis through the expression and activation of matrix metalloproteinases.
In order to investigate the role of macrophages in glomeruli in the progression of glomerular sclerosis, methyl-cellulose (MC) was administered intraperitoneally to Wistar rats, in addition to intravenous injection of anti-thy1-1 antibody. In this group of rats (Thy-1 + MC group), many macrophages infiltrated in the lytic mesangium accompanied by rupture of capillary loops at an early stage and stayed with abundant deposition of mesangial matrices until day 35, whereas the proliferative lesions following mesangiolysis almost vanished in the rats treated with anti-thy1-1 antibody alone (Thy-1 group). In immunostaining, matrix metalloproteinase (MMP)-9 was expressed along regenerating capillaries of the Thy-1 group and in extracapillary lesions of the Thy-1 + MC group after day 7. In gelatin zymography, the gelatinolytic band for MMP-9 was expressed much more strongly in the Thy-1 + MC group than in the Thy-1 group at day 3, but it was expressed a little more strongly in the Thy-1 group than in the Thy-1 + MC group at day 7. The bands for an active form of MMP-2 were more strongly expressed in the Thy-1 + MC group than in the Thy-1 group throughout the experimental period. These results suggest that persistent accumulation of macrophages in mesangium induces glomerular sclerosis through expression and activation of MMP.
Shiozawa
S
S
First Department of Pathology, Shinshu University School of Medicine, Matsumoto, Japan.
D000818:Animals; D005780:Gelatin / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000201:enzymology / Q000473:pathology*; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D008264:Macrophages / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D016482:Urinalysis
D019715:Tissue Inhibitor of Metalloproteinase-1; D005780:Gelatin; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9