Effect of TJN-331 on anti-Thy1 nephritis in rats via inhibition of transforming growth factor-β1 production.

Abstract:

:This study was performed to examine the effects of the antifibrotic agents TJN-331 and tranilast on mesangial expansion in a rat model of anti-Thy1 nephritis. We first investigated the effects of TJN-331 and tranilast on mesangial expansion induced by anti-Thy1 serum in rats, and determined the counts of glomerular cells and proliferative cell nuclear antigen (PCNA)-positive cells. The effects of TJN-331 and tranilast on production of transforming growth factor-β1 (TGF-β1) by isolated glomeruli incubated for 48 h were then examined. The TGF-β1 staining score, the number of TGF-β1-positive cells and the TGF-β1 receptor-positive area in the anti-Thy1 nephritis model were also measured using immunohistochemistry. TJN-331 administered from day 1 (the day after anti-Thy1 serum injection) blocked an increase in mesangial matrix accumulation on days 4 and 8, compared to untreated anti-Thy1 nephritic rats. TJN-331 also inhibited both the increase in the number of glomerular cells on day 8 and the decrease in this cell count on day 2 observed in untreated nephritic rats, and TJN-331 and tranilast inhibited an increase in PCNA-positive cells in the glomerular cross section on days 4 and 8. Both TJN-331 and tranilast inhibited increases in the TGF-β1 protein content from nephritic glomeruli, the TGF-β1-positive area, and the number of TGF-β1-positive cells/cross section in anti-Thy1 nephritic glomeruli. These results suggest that TJN-331 and tranilast prevent expansion of the mesangial area by suppression of TGF-β1 secretion from inflamed glomeruli.

journal_name

Biol Pharm Bull

authors

Saegusa Y,Sadakane C,Koseki J,Hasegawa Y,Shindo S,Maruyama H,Kase Y,Takeda S,Takeda H,Hattori T

doi

10.1248/bpb.33.1710

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

1710-5

issue

10

eissn

0918-6158

issn

1347-5215

pii

JST.JSTAGE/bpb/33.1710

journal_volume

33

pub_type

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