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- Title
Glomerular activin A overexpression is linked to fibrosis in anti-Thy1 glomerulonephritis.
- Authors
Jens Gaedeke; Torsten Boehler; Klemens Budde; Hans-H. Neumayer; Harm Peters
- Abstract
Background. Activin A, a member of the transforming growth factor- (TGF-) superfamily of proteins, shares many biological features with the pro-fibrotic cytokine TGF-1, which is primarily responsible for the accumulation of extracellular matrix proteins in renal disease. This study was designed to identify regulators of activin A production in glomerular mesangial cells and test if activin A acts as a pro-fibrotic cytokine in mesangial cells.Methods. The effect of inflammatory cytokines on activin A production and the effect of exogenous activin A on mediators of fibrosis were analysed in cultured rat mesangial cells. Expression of activin A and of established mediators of fibrosis was analysed in a rat model of glomerular fibrosis (anti-Thy1 glomerulonephritis).Results. In cultured mesangial cells, interleukin-1 and basic fibroblast growth factor, both mediators of glomerular inflammatory injury, dose-dependently increased activin A expression. Incubation with activin A significantly stimulated TGF-1, PAI-1 and connective tissue growth factor RNA expression and increased production of extracellular matrix proteins in mesangial cells. In rats with anti-Thy1 glomerulonephritis, expression of glomerular activin A mRNA and protein paralled the expression of TGF- and other indices of fibrosis, showing little change from normal on day 1, a marked, 70-fold increase of activin protein production on day 6, and a subsequent decrease at day 12. Antifibrotic therapy with the angiotensin-converting enzyme inhibitor enalapril significantly reduced glomerular activin A production.Conclusion. Taken together, the results of this study link overexpression of activin A to glomerular matrix protein expansion in vivo and in vitro, suggesting that activin A acts as pro-fibrotic cytokine in renal disease.
- Subjects
KIDNEY diseases; TRANSFORMING growth factors-beta; EXTRACELLULAR matrix proteins; CYTOKINES
- Publication
Nephrology Dialysis Transplantation, 2005, Vol 20, Issue 2, p319
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfh653