TJN-331 improves anti-glomerular basement membrane nephritis by inhibiting the production of intraglomerular transforming growth factor-beta1.
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.
Saegusa
Yayoi
Y
Tsumura Research Laboratories, Tsumura & Co., Ibaraki 300-1192, Japan.
Sadakane
Chiharu
C
Koseki
Junichi
J
Hasegawa
Yoshihiro
Y
Shindo
Shoichiro
S
Maruyama
Hirobumi
H
Takeda
Shuichi
S
Takeda
Hiroshi
H
Hattori
Tomohisa
T
D000178:Acrylamides / Q000008:administration & dosage / Q000627:therapeutic use*; D000199:Actins / Q000378:metabolism; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000652:urine; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D015394:Molecular Structure; D011507:Proteinuria / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control / Q000652:urine; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
D000178:Acrylamides; D000199:Actins; D003404:Creatinine; D011725:Pyridines; D053773:Transforming Growth Factor beta1; C554102:N-(3,4-dimethoxyphenethyl)-N-methyl-3-(3-pyridyl)-2-propenamide; C498862:Acta2 protein, rat