Mast cells decrease renal fibrosis in unilateral ureteral obstruction

Abstract

Mast cells regulate both inflammatory responses and tissue repair in human diseases but there are conflicting reports on the role of these cells in the pathogenesis of various kidney diseases. Here we measured mast cell function in unilateral ureteral obstruction, a well-characterized model of renal fibrosis, using Kit(W)/Kit(W-v) mice genetically deficient in mast cells, wild-type mice, and deficient mice reconstituted by adoptive transfer with mast cells from the wild-type animals. Mast cell-deficient mice had higher levels of renal tubular damage, more stromal fibrosis, higher numbers of infiltrating ERHR3-positive macrophages and CD3-positive T cells, and higher tissue levels of profibrotic transforming growth factor-beta1 than wild-type mice or mice reconstituted by adoptive transfer of mast cells 3 weeks after ureteral obstruction. Similarly, while wild-type and adoptively transferred mice had increased alpha-smooth muscle actin and decreased E-cadherin expression, which are indicators of epithelial-mesenchymal transition, the obstructed kidneys of the mast cell-deficient mice had significant attenuation of those indicators. Thus, our study suggests that mast cells protect the kidney against fibrosis by modulation of inflammatory cell infiltration and by transforming growth factor-beta1-driven epithelial-to-mesenchymal transitions.

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).…”

A reduction of unilateral ureteral obstruction-induced renal fibrosis by a therapy combining valsartan with aliskiren

“…The model of unilateral ureteral obstruction (UUO) generates progressive renal fibrosis that is independent of hypertension or systemic immune disease (8,26). The obstructed kidney after UUO results in marked renal hemodynamic and metabolic changes.…”

Erythropoietin ameliorates renal interstitial fibrosis via the inhibition of fibrocyte accumulation

“…Western blot analysis was performed as previousy described (21). In brief, protein samples were heated at 100˚C for 5 min and subjected to electrophoresis on 10 or 15% SDS gels.…”