title: Tranilast ameliorates experimental mesangial proliferative glomerulonephritis.
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-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, St. Vincent's Hospital, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Tokuyama
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Kelly
authors.forename: Alison
authors.initials: A
authors.lastname: Cox
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kerri
authors.initials: K
authors.lastname: Thai
authors.forename: David J
authors.initials: DJ
authors.lastname: Nikolic-Paterson
authors.forename: Richard E
authors.initials: RE
authors.lastname: Gilbert
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D004195:Disease Models, Animal; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy* / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D062367:ortho-Aminobenzoates / Q000008:administration & dosage*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D062367:ortho-Aminobenzoates; C012293:tranilast