Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mast cells are involved in chronic inflammation and tissue fibrosis. To determine whether these cells are also involved in tubulointerstitial injury in glomerulonephritis, we assayed mast cell infiltration in the kidneys of 107 patients with primary or secondary glomerulonephritis. Using a monoclonal antihuman tryptase antibody, we detected mast cells in the renal cortical tubulointerstitium, the periglomerular areas, and the medullary interstitium, but not in glomeruli. Renal cortical tubulointerstitial mast cells, including periglomerular area, were estimated as 0.8+/-1.6 cells/mm2 in minimal change nephrotic syndrome (n=7), 1.5+/-0.7 cells/mm2 in minor glomerular abnormalities without nephrotic syndrome (n=7), 6.5+/-7.7 cells/mm2 in membranous nephropathy(n=10), 12.9+/-15.5 cells/mm2 in lupus nephritis (n=15), 13.4+/-8.3 cells/mm2 in focal segmental glomerular sclerosis (n=6), 18.5+/-21.1 cells/mm2 in ANCA-related nephropathy (n=5), 19.8+/-14.2 cells/mm2 in membranoproliferative glomerulonephritis (n=5), 21.3+/-17.7 cells/mm2 in immunoglobulin A (IgA) nephropathy (n=42), and 33.0+/-33.8 cells/mm2 in diabetic nephropathy (n=10). Except for patients with the rapidly progressive glomerulonephritic syndrome (RPGN), the number of infiltrating mast cells significantly correlated with the serum concentration of creatinine at the time of renal biopsy (r=0.59; P < 0.0001) and with the intensity of tubulointerstitial injury as measured by leukocyte infiltration (r=0.72; P < 0.0001) and fibrosis (r=0.75; P < 0.0001). In contrast, mast cell infiltration did not correlate with urinary protein excretion. In relation to serum creatinine concentration, the number of mast cells was fewer in patients with RPGN than in those with chronic glomerulonephritis. These data suggest that mast cells may contribute to the renal deterioration in glomerulonephritis by inducing chronic tubulointerstitial injury.
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PMID:Tubulointerstitial mast cell infiltration in glomerulonephritis. 977 20

Renal interstitial fibrosis is characterized by increased proliferation of fibroblasts and excessive accumulation of extracellular matrix. Mast cell tryptase has been implicated in the development of tissue fibrosis in skin and lungs. However, the significance of mast cell tryptase in human renal diseases has not been investigated. The potential role of mast cell-derived tryptase in the development of renal fibrosis was studied using immunohistochemical techniques and cultured human renal fibroblast cell lines. Semiquantitative immunostaining analysis of samples from 70 patients with several renal diseases, including IgA glomerulonephritis (GN) (n = 30), non-IgA GN (n = 5), membranous GN (n = 5), focal segmental glomerulosclerosis (n = 4), minor glomerular abnormalities (n = 5), lupus nephritis (n = 3), and acute or chronic tubulointerstitial nephritis (n = 18), revealed that the degree of renal interstitial fibrosis was well correlated with the number of infiltrating tryptase-positive mast cells (P < 0.01). Mast cells could not be detected in damaged glomeruli in any form of renal disease. [(3)H]Thymidine uptake experiments demonstrated that DNA synthesis by cultured renal fibroblasts was increased with the concentration of tryptase (0.5 to 5 nM) coincubated with heparin and was suppressed by coincubation with the protease inhibitors leupeptin and benzamidine hydrochloride. Tryptase alone also increased DNA synthesis by fibroblasts but exhibited less effectiveness, compared with the combination of tryptase and heparin. Conversely, heparin alone suppressed DNA synthesis by fibroblasts. Metabolic [(35)S]methionine-labeling experiments with cultured renal fibroblasts indicated that tryptase increased the synthesis of fibronectin and collagen type I, in a dose-dependent manner. These findings suggest that mast cell tryptase plays a role in the proliferation and extracellular matrix protein production of renal interstitial fibroblasts and thus contributes to the development of renal interstitial fibrosis.
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PMID:Role of mast cell tryptase in renal interstitial fibrosis. 1146 39

IgA nephropathy is generally considered to be an immune-complex-mediated or aggregated (polymerized) IgA (IgA1)-mediated glomerulonephritis. Since the pathogenesis of IgA nephropathy is still obscure, it is important to determine the initiation and progression of this disease using the spontaneous animal model. The ddY mouse strain can serve as a spontaneous animal model for IgA nephropathy. Genetic factors are considered to be involved in the initiation and progression of IgA nephropathy. It has been hypothesized that susceptibility genes for IgA nephropathy can be detected by a genome-wide scan using this model. The peak marker D10MIT 86 on chromosome 10 is located on the region syntenic to human 6q22-23 with IGAN1, which is responsible for familiar IgA nephropathy. There are several developmental and/or exacerbating factors in this disease. Among them, the loss of glomerular epithelial cells (podocytes) and interstitial mast cell infiltration are important factors for progression of glomerulosclerosis and tubulointerstitial injury in patients with IgA nephropathy.
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PMID:Pathogenesis of IgA nephropathy. 1749 30