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
JournalNephron - Experimental Nephrology
Volume109
Issue number1
DOIs
Publication statusPublished - 2008 Jun
Externally publishedYes

Fingerprint

Glomerulonephritis
Mesangial Cells
Platelet-Derived Growth Factor
IGA Glomerulonephritis
Transforming Growth Factors
Proline
Thymidine
Glomerular Mesangium
Collagen Type IV
Nephritis
tranilast
Proteinuria
Smooth Muscle
Wistar Rats
Actins
Cultured Cells
Intercellular Signaling Peptides and Proteins
Collagen
Animal Models
Macrophages

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

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). https://doi.org/10.1159/000131752

Tranilast ameliorates experimental mesangial proliferative glomerulonephritis. / Tokuyama, Hirobumi; Kelly, Darren J.; Cox, Alison; Zhang, Yuan; Thai, Kerri; Nikolic-Paterson, David J.; Gilbert, Richard E.

In: Nephron - Experimental Nephrology, Vol. 109, No. 1, 06.2008.

Research output: Contribution to journalArticle

Tokuyama, H, Kelly, DJ, Cox, A, Zhang, Y, Thai, K, Nikolic-Paterson, DJ & Gilbert, RE 2008, 'Tranilast ameliorates experimental mesangial proliferative glomerulonephritis', Nephron - Experimental Nephrology, vol. 109, no. 1. https://doi.org/10.1159/000131752
Tokuyama, Hirobumi ; Kelly, Darren J. ; Cox, Alison ; Zhang, Yuan ; Thai, Kerri ; Nikolic-Paterson, David J. ; Gilbert, Richard E. / Tranilast ameliorates experimental mesangial proliferative glomerulonephritis. In: Nephron - Experimental Nephrology. 2008 ; Vol. 109, No. 1.
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AU - Nikolic-Paterson, David J.

AU - Gilbert, Richard E.

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AB - 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.

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