Effect of vasopressin on type IV collagen production in human mesangial cells.
Production of extracellular matrix proteins, such as type IV collagen and fibronectin, by mesangial cells contributes to progressive glomerulosclerosis. In this study, the ability of vasopressin (AVP), which causes mesangial cell proliferation and hypertrophy, to stimulate type IV collagen production by cultured human mesangial cells was examined using an enzyme-linked immunosorbent assay. AVP induced a concentration-dependent increase in the production of type IV collagen and this effect was potently and concentration-dependently inhibited by AVP V1A receptor antagonists, including YM218. AVP also induced a concentration-dependent increase in transforming growth factor (TGF)-beta secretion by human mesangial cells and this effect was inhibited by V1A receptor antagonists. Furthermore, TGF-beta also induced an increase in the production of type IV collagen; the AVP-enhanced production of type IV collagen was inhibited by an anti-TGF-beta antibody. These findings indicate that AVP stimulates synthesis of type IV collagen by cultured human mesangial cells through the induction of TGF-beta synthesis mediated by V1A receptors; consequently, AVP contributes to glomerular remodeling and extracellular matrix accumulation observed in glomerular diseases.
Tahara
Atsuo
A
Institute for Drug Discovery Research, Astellas Pharma Inc., 5-2-3, Toukoudai, Tsukuba, Ibaraki 300-2698, Japan. atsuo.tahara@jp.astellas.com
Tsukada
Junko
J
Tomura
Yuichi
Y
Suzuki
Takeshi
T
Yatsu
Takeyuki
T
Shibasaki
Masayuki
M
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000494:pharmacology; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology*
C501286:4'-(4,4-difluoro-5-(2-oxo-2-(4-piperidinopiperidino)ethylidene)-2,3,4,5-tetrahydro-1H-1-benzoazepine-1-carbonyl)-2-methyl-3-furanilide; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D024141:Collagen Type IV; D010880:Piperidines; D016212:Transforming Growth Factor beta; D014667:Vasopressins