TJN-331 improves anti-glomerular basement membrane nephritis by inhibiting the production of intraglomerular transforming growth factor-beta1.

Abstract:

:Transforming growth factor-beta1 (TGF-beta1) plays an important role in the development of glomerulonephritis. The study of experimental glomerulonephritis in rats was performed to examine the antinephritic effects of TJN-331, a new herbally-derived chemical compound. To clarify the action of TJN-331 ((E)-N-(3,4-dimethoxyphenethyl)-N-methyl-3-(3-pyridyl)-2-propenamide) on TGF-beta1 production, glomeruli were isolated from rats with antiglomerular basement membrane (GBM) nephritis and incubated for 48 h with test drugs in vitro. Next, we examined the effects of TJN-331 on rat anti-GBM nephritis induced by injection with anti-GBM serum. TJN-331 dose-dependently inhibited the increase in total and mature TGF-beta1 production from nephritic glomeruli, although it did not inhibit TGF-beta1 production from normal glomeruli. Administration of TJN-331, at a dose of 2 mg/kg/d, per os (p.o.), prevented proteinuria and increased crescent formation and adhesion of capillary walls to Bowman's capsule. The increases in mature TGF-beta1 protein production and TGF-beta1 staining score in nephritic rats were reversed by TJN-331 treatment. These results suggest that TJN-331 inhibits proteinuria and histopathological changes in glomeruli via suppression of TGF-beta1 production from inflamed glomeruli.

journal_name

Biol Pharm Bull

authors

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

doi

10.1248/bpb.33.1349

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

1349-54

issue

8

eissn

0918-6158

issn

1347-5215

pii

JST.JSTAGE/bpb/33.1349

journal_volume

33

pub_type

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