Role of mast cells in the development of renal fibrosis: Use of mast cell–deficient rats

Abstract

Role of mast cells in the development of renal fibrosis: Use of mast cell-deficient rats.Background. Recent clinical studies have shown that the number of interstitial mast cells increases in various types of renal disease and correlates well with the magnitude of interstitial fibrosis. The present study was conducted to assess the role of mast cells in renal fibrosis by examining an experimental glomerular disease.Methods. A rat model of chronic glomerular disease, puromycin aminonucleoside-nephrosis, was induced in mast cell-deficient (Ws/Ws) and normal (+/+) rats.Results. The area of interstitial fibrosis was widely distributed at 6 weeks in both groups of rats; however, unexpectedly, the area of interstitial fibrosis was greater in Ws/Ws rats than in +/+ littermates. Biochemical analysis of the hydroxyproline content confirmed the more severe fibrosis in the Ws/Ws rats. The number of mast cells increased in both Ws/Ws and +/+ rats, concomitant with the development of interstitial fibrosis, but was confirmed to be lower in Ws/Ws than in +/+ rats. There were no differences in the numbers of interstitial macrophages and T lymphocytes between the two groups. Reverse transcriptionpolymerase chain reaction analysis of cytokine expression revealed that the level of mRNA for transforming growth factorb (TGF-b), a potent profibrotic cytokine, was higher in Ws/Ws rats. In addition, heparin, one of the major components of mast cells, inhibited the expression of TGF-b mRNA in rat fibroblasts in culture.Conclusion. These results suggest that mast cells do not play a major role in the pathogenesis of interstitial fibrosis in puromycin aminonucleoside nephrosis. Rather, they might be protective or ameliorative in this model through the inhibition of TGF-b production by heparin, and possibly in other models and also in humans.Mast cells are known to be immune-effector cells that augment inflammatory reactions. It is widely accepted

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…Most studies have suggested that a reduction of mast cells, or their typical enzyme chymase, increases fibrosis (52)(53)(54)(55)(56), whereas others suggest the opposite (57,58). Thus, the potential therapeutic value of mast cell manipulation in fibrosis is uncertain (23,59).…”

Role of Mast Cells in Progressive Renal Diseases

“…In vitro experiments showed that heparin inhibited the expression of mRNA encoding TGF-␤ in cultured rat fibroblasts. 91 Preliminary studies in a murine model of ureteral obstruction also suggested that mast cells protect against fibrosis. 92 Thus, data from experimental mast cell-deficient mice do not support the attractive hypothesis that mast cells play a profibrotic role in chronic renal disease.…”

A Pathogenetic Role for Mast Cells in Experimental Crescentic Glomerulonephritis

“…In pristane-induced experimental lupus nephritis, mast cell-deficient mice developed equivalent renal disease to WT mice (27). A slightly protective role for mast cells in the development of fibrosis was suggested in rats 6 wk after the induction of puromycin aminonucleoside nephritis (28). A functional role of mast cells in the pathogenesis of crescentic GN has not been established.…”