Tranilast ameliorates experimental mesangial proliferative glomerulonephritis

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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-β (TGF-β). Tranilast [n-(3,4-dimethoxycinnamoyl) anthranilic acid] has been shown to block the actions of PDGF and TGF-β. 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 μM) was determined by 3H-proline and 3H-thymidine incorporation, respectively. Results: Tranilast treatment resulted in a significant reduction in mesangial cell proliferation, macrophage infiltration, activated (α-smooth muscle actin positive) mesangial cells, glomerular type IV collagen deposition and proteinuria compared to control rats. Also, PDGF stimulation of mesangial cell 3H-thymidine and 3H-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.

Original languageEnglish
Pages (from-to)e1-e7
JournalNephron - Experimental Nephrology
Volume109
Issue number1
DOIs
Publication statusPublished - 2008 Jun 1
Externally publishedYes

Keywords

  • Cell proliferation
  • Mesangial cells
  • Platelet-derived growth factor
  • Tranilast

ASJC Scopus subject areas

  • Physiology
  • Genetics
  • Nephrology

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    Tokuyama, H., Kelly, D. J., Cox, A., Zhang, Y., Thai, K., Nikolic-Paterson, D. J., & Gilbert, R. E. (2008). Tranilast ameliorates experimental mesangial proliferative glomerulonephritis. Nephron - Experimental Nephrology, 109(1), e1-e7. https://doi.org/10.1159/000131752