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Renal fibrosis is the final common pathway of most progressive renal diseases.
Renal tubular cell expression of the C5a R was sparse in normal cortex but markedly upregulated after UUO.
Treatment of wild-type UUO mice with C5a RA also led to a significant reduction of cortical Sirius Red staining, fibronectin protein expression, and PDGF-B m RNA expression on day 5.
Neither genetic C5 deficiency nor C5a RA treatment caused any histologic changes in the nonobstructed kidneys.
In cultured murine cortical tubular cells, C5a stimulated production of TGF-β, and this was inhibited by C5a RA.
Using a combined genetic and pharmacologic approach, C5, in particular C5a, is identified as a novel profibrotic factor in renal disease and as a potential new therapeutic target.
Interstitial renal fibrosis is the common end point of progressive kidney diseases.The identification of mediators that are involved in this process could lead to novel therapeutic approaches.It is well established that activation of downstream components of the complement cascade such as C5, C6, or the membrane attack complex C5b-9 is involved in many renal diseases (reviewed in reference ).For example, elevated urinary C5b-9 concentrations are found in proteinuric patients (2), urinary C5b-9 was shown to reflect disease activity in an experimental model of membranous glomerulonephritis better then proteinuria (3), C5b-9 depletion in experimental nephropathy reduces proteinuria (4), and C5b-9 is formed at sites of tubulointerstitial injury (5,6).In proteinuric animal models such as mesangioproliferative glomerulonephritis, Adriamycin nephropathy, five-sixths nephrectomy, and puromycin aminonucleoside nephrosis, complement depletion or the lack of C6 ameliorated tubulointerstitial injury (7–11).In experimental immune-complex glomerulonephritis, lack of the C5a receptor (C5a R) reduced infiltrating interstitial cells and tubulointerstitial damage but had no influence on glomerular injury, thereby pointing to a role of the anaphylatoxin C5a, a small peptide that is released from C5, in tubulointerstitial injury (12).Tags: Adult Dating, affair dating, sex dating