Tranilast ameliorates experimental mesangial proliferative glomerulonephritis

Hirobumi Tokuyama, Darren James Kelly, Alison Cox, Yuan Zhang, Kerri Thai, David J Nikolic-Paterson, Richard E Gilbert

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10 Citations (Scopus)


BACKGROUND: Immunoglobulin A nephropathy and its related animal model Thy1.1 nephritis are characterized by mesangial hypercellularity, extracellular matrix expansion and overexpression of the proproliferative and profibrotic growth factors, platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta). Tranilast [n-(3,4-dimethoxycinnamoyl) anthranilic acid] has been shown to block the actions of PDGF and TGF-beta. METHODS: Experimental mesangial proliferative glomerulonephritis was induced in male Wistar rats with a monoclonal anti-rat Thy-1.1 antibody (OX-7) with rats randomized to receive either tranilast 400 mg/kg/day or vehicle control. Collagen synthesis and proliferation of cultured mesangial cells following incubation with PDGF (50 ng/ml) and tranilast (10-100 microM) was determined by (3)H-proline and (3)H-thymidine incorporation, respectively. RESULTS: Tranilast treatment resulted in a significant reduction in mesangial cell proliferation, macrophage infiltration, activated (alpha-smooth muscle actin positive) mesangial cells, glomerular type IV collagen deposition and proteinuria compared to control rats. Also, PDGF stimulation of mesangial cell (3)H-thymidine and (3)H-proline incorporation was reduced by tranilast in a dose-dependent manner. CONCLUSION: These in vitro data and the amelioration of the pathological findings of experimental mesangial proliferative glomerulonephritis by tranilast suggest the potential clinical utility of this approach as a therapeutic strategy in mesangial proliferative conditions such as immunoglobulin A nephropathy. Copyright 2008 S. Karger AG, Basel.
Original languageEnglish
Pages (from-to)1 - 7
Number of pages7
JournalNephron Experimental Nephrology
Issue number1
Publication statusPublished - 2008
Externally publishedYes

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