(E)-N-[(3,4-dimethoxyphenethyl)]-N-methyl-3-(3-pyridyl)-2-propenamide (TJN-331) inhibits mesangial expansion in experimental IgA nephropathy in ddY mice.

Abstract

BACKGROUND:

TJN-331 is an inhibitor of transforming growth factor β1 (TGF-β1) production that has similar structural features to the natural product acteoside. This study was performed to examine the antinephritic effects of TJN-331 in a mouse model of experimental IgA nephropathy.

MATERIALS AND METHODS:

IgA nephropathy was induced in ddY mice by oral administration of bovine γ globulin, followed by reticuloendothelial blocking by colloidal carbon injection and heminephrectomy. Effects of TJN-331 were examined over oral administration periods from 10 to 15 weeks after the third colloidal carbon injection. Intravenous administration of a TGF-β1-neutralizing antibody was used to investigate the role of TGF-β1 in IgA nephropathy.

RESULTS:

Administration of TJN-331 or captopril prevented elevation of serum creatinine. Histopathological examination after both experimental periods showed that TJN-331 inhibited increases in the mesangial matrix index and the number of nuclei per glomerular cross-section, compared with in untreated ddY mice with IgA nephropathy. TJN-331 prevented increase in glomerular TGF-β1 staining without affecting IgA. In the in vitro study, TJN-331 prevented total TGF-β1 production from splenocytes stimulated with concanavalin A. A neutralizing antibody against TGF-β1 prevented increase in the mesangial matrix index and the number of glomerular cells per cross-sectional area.

CONCLUSION:

These results suggest that TJN-331 is effective against IgA nephropathy in ddY mice and acts via suppression of TGF-β1 production in glomeruli.

• Authors: Yayoi Saegusa, Chiharu Sadakane, Junichi Koseki, Yoshihiro Hasegawa, Shoichiro Shindo, Shuichi Takeda, Hiroshi Takeda, Tomohisa Hattori
• Journal: Clinical and experimental nephrology (Clin Exp Nephrol) Vol. 14 Issue 6 Pg. 528-35 (Dec 2010) ISSN: 1437-7799 [Electronic] Japan
• PMID: 20814808 (Publication Type: Journal Article)

Chemical References

• Acrylamides
• N-(3,4-dimethoxyphenethyl)-N-methyl-3-(3-pyridyl)-2-propenamide
• Pyridines
• Transforming Growth Factor beta1
• Concanavalin A
• Creatinine

Topics

• Acrylamides (pharmacology)
• Animals
• Concanavalin A (pharmacology)
• Creatinine (blood)
• Disease Models, Animal
• Glomerular Mesangium (drug effects, pathology)
• Glomerulonephritis, IGA (pathology)
• Kidney Glomerulus (pathology)
• Mice
• Mice, Inbred Strains
• Nephrectomy
• Pyridines (pharmacology)
• Spleen (cytology)
• Transforming Growth Factor beta1 (antagonists & inhibitors, biosynthesis)