Participation of macrophages in glomerular sclerosis through the expression and activation of matrix metalloproteinases

Abstract

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.

Matrix Metalloproteinases and Their Inhibitions in Experimental Renal Scarring

“…However, while tubular cells have the ability to produce most MMPs, production is generally low both in cell lines and primary culture (personal observation, TSJ). It would therefore seem more likely that MMP increases result from up-regulation around infiltrating cells such as fibroblasts or macrophages, both of which produce large quantities of particularly MMP-1 [53, 55, 56, 66]. Although one must still consider that some of the MMP regulation could be specific compartmentalised remodelling such as in the glomerulus where there are a number of studies showing up-regulation of gelatinases in mesangial cells [4]in various nephropathies.…”

Renal Redox Stress and Remodeling in Metabolic Syndrome, Type 2 Diabetes mellitus, and Diabetic Nephropathy: Paying Homage to the Podocyte

“…The multiple metabolic A-FLIGHT-U toxicities acronym was created to enable the reader to better understand the relationship of the multiple toxicities to the development of renal redox stress, ROS and renal cellular and extracellular matrix remodeling [27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65]. …”

Insights into the mechanisms of renal fibrosis: is it possible to achieve regression?

“…Several recent studies correlated the development of renal fibrosis with activation of metalloproteinases (34,63). Studies testing the efficiency of MMP inhibitor treatment during renal fibrosis gave contradictory results.…”