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Tranilast ameliorates experimental mesangial proliferative glomerulonephritis
Hirobumi Tokuyama1, Darren J Kelly, Alison Cox
1Department of Medicine, St. Vincent's Hospital, University of Melbourne, Melbourne, Vic., Australia.
Nephron. Experimental Nephrology
|May 16, 2008
Summary
Tranilast significantly reduced mesangial cell proliferation and kidney damage in a rat model of glomerulonephritis. This suggests tranilast may be a potential therapy for conditions like immunoglobulin A nephropathy.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Immunoglobulin A nephropathy and Thy1.1 nephritis share features like mesangial hypercellularity and expansion.
- These conditions involve overexpression of platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta).
- Tranilast is known to inhibit the actions of PDGF and TGF-beta.
Purpose of the Study:
- To investigate the therapeutic potential of tranilast in experimental mesangial proliferative glomerulonephritis.
- To evaluate tranilast's effects on cell proliferation, collagen synthesis, and kidney damage markers.
Main Methods:
- Experimental mesangial proliferative glomerulonephritis was induced in Wistar rats using an anti-rat Thy-1.1 antibody.
- Rats were treated with either tranilast (400 mg/kg/day) or a vehicle control.
- In vitro studies assessed tranilast's effect on PDGF-stimulated mesangial cell proliferation and collagen synthesis.
Main Results:
- Tranilast treatment significantly reduced mesangial cell proliferation, macrophage infiltration, and alpha-smooth muscle actin positive cells.
- Glomerular type IV collagen deposition and proteinuria were also significantly decreased in tranilast-treated rats.
- In vitro, tranilast dose-dependently inhibited PDGF-stimulated mesangial cell proliferation and collagen synthesis.
Conclusions:
- In vitro and in vivo data suggest tranilast ameliorates pathological findings in experimental glomerulonephritis.
- Tranilast shows potential as a therapeutic strategy for mesangial proliferative diseases, including immunoglobulin A nephropathy.