Title:Impact of Mast Cell Chymase on Renal Disease Progression
Volume: 8
Issue: 1
Author(s): Haimanot Wasse, Nawazish Naqvi and Ahsan Husain
Affiliation:
Keywords:
Chymase, mast cells, kidney disease, angiotensin II, transforming growth factor-β, cytosol, tubulointerstitial disease, mast cell proliferation, inflammatory mediators
Abstract: Chymase, a serine protease found in mast cell granules, is released into the interstitium following injury or
inflammation. Chymase is the primary ACE-independent pathway of angiotensin II formation, and also functions to
activate TGF-beta and other promoters of extracellular matrix degradation, thereby playing a role in tissue remodeling. In
the diseased kidney, chymase-containing mast cells markedly increase and their density correlates with tubulointerstitial
fibrosis severity. Studies in humans support the pathologic role of chymase in diabetic nephropathy, while animal studies
form the basis for the importance of increased chymase-dependent angiotensin II formation in progressive hypertensive,
diabetic and inflammatory nephropathies. Moreover, humans with kidney disease express chymase in diseased blood
vessels in concordance with significantly elevated plasma chymase levels. Conversely, specific chymase inhibitors
attenuate angiotensin II production and renal fibrosis in animal models, suggesting their potential therapeutic benefit in
human nephropathy, where chymase-containing mast cells accumulate and contribute to progressive disease.
