Vasopressin increases type IV collagen production through the induction of transforming growth factor-beta secretion in rat mesangial cells.
Production of extracellular matrix proteins, such as type IV collagen, by mesangial cells contributes to progressive glomerulosclerosis. Transforming growth factor-beta (TGF-beta) modulates mesangial cell growth and stimulates extracellular matrix synthesis by mesangial cells. In this study, the ability of vasopressin (AVP), which causes mesangial cell proliferation and hypertrophy, to stimulate type IV collagen production and correlation with TGF-beta secretion by cultured rat mesangial cells was examined. AVP induced a time- and concentration-dependent increase in TGF-beta secretion and mitogenic effect in rat mesangial cells. This AVP-induced increase in TGF-beta secretion was potently inhibited by AVP V(1A) receptor-selective antagonist. AVP also induced a concentration-dependent increase in the production of type IV collagen and this effect was inhibited by V(1A) receptor-selective antagonist. 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 results demonstrate that AVP stimulates synthesis of type IV collagen by cultured rat mesangial cells through the induction of TGF-beta synthesis mediated by V(1A) receptors. Therefore, AVP-induced TGF-beta secretion by proliferating mesangial cells might act as an autocrine factor to regulate synthesis of extracellular matrix; this mechanism may contribute to glomerulosclerosis in renal diseases including diabetic nephropathy.
Tahara
Atsuo
A
Institute for Drug Discovery Research, Astellas Pharma Inc, Tsukuba, Ibaraki, Japan. atsuo.tahara@jp.astellas.com
Tsukada
Junko
J
Tomura
Yuichi
Y
Yatsu
Takeyuki
T
Shibasaki
Masayuki
M
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000494:pharmacology / Q000502:physiology*; D001552:Benzazepines / Q000494:pharmacology; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013141:Spiro Compounds / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000378:metabolism*
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; D009025:Morpholines; D010880:Piperidines; D013141:Spiro Compounds; D016212:Transforming Growth Factor beta; D001127:Arginine Vasopressin; C103281:satavaptan