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.

• Authors: Yayoi Saegusa, Chiharu Sadakane, Junichi Koseki, Yoshihiro Hasegawa, Shoichiro Shindo, Hirobumi Maruyama, Shuichi Takeda, Hiroshi Takeda, Tomohisa Hattori
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 33 Issue 8 Pg. 1349-54 ( 2010) ISSN: 1347-5215 [Electronic] Japan
• PMID: 20686230 (Publication Type: Journal Article)

Chemical References

• Acrylamides
• Actins
• N-(3,4-dimethoxyphenethyl)-N-methyl-3-(3-pyridyl)-2-propenamide
• Pyridines
• Transforming Growth Factor beta1
• smooth muscle actin, rat
• Creatinine

Topics

• Acrylamides (administration & dosage, therapeutic use)
• Actins (metabolism)
• Animals
• Anti-Glomerular Basement Membrane Disease (blood, drug therapy, metabolism, urine)
• Creatinine (blood)
• Disease Models, Animal
• Gene Expression (drug effects)
• Immunohistochemistry
• Kidney Glomerulus (drug effects, metabolism, pathology)
• Male
• Molecular Structure
• Proteinuria (metabolism, pathology, prevention & control, urine)
• Pyridines (administration & dosage, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Transforming Growth Factor beta1 (antagonists & inhibitors, biosynthesis, genetics)