Tranilast ameliorates experimental mesangial proliferative glomerulonephritis.
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.
Tokuyama
Hirobumi
H
Department of Medicine, St. Vincent's Hospital, University of Melbourne, Melbourne, Vic., Australia.
Kelly
Darren J
DJ
Cox
Alison
A
Zhang
Yuan
Y
Thai
Kerri
K
Nikolic-Paterson
David J
DJ
Gilbert
Richard E
RE
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*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D062367:ortho-Aminobenzoates; C012293:tranilast