title: Vasopressin regulates rat mesangial cell growth by inducing autocrine secretion of vascular endothelial growth factor.
abstract: Mesangial cell growth is a key feature of several glomerular diseases. Vascular endothelial growth factor (VEGF) is a potent mitogen of vascular endothelial cells and promoter of vascular permeability. Here, we examined the ability of vasopressin (AVP), which causes mesangial cell proliferation and hypertrophy, to stimulate VEGF secretion from cultured rat mesangial cells. AVP potently induced a time- and concentration-dependent increase in VEGF secretion in these cells, which was then inhibited by a V(1A) receptor-selective antagonist, confirming this is a V(1A) receptor-mediated event. VEGF also induced hyperplasia and hypertrophy in mesangial cells, which was completely abolished by an anti-VEGF antibody. In addition, AVP-induced hyperplasia and hypertrophy were completely inhibited by the V(1A) receptor-selective antagonist and partially abolished by the anti-VEGF antibody. These results indicate that AVP increases VEGF secretion in rat mesangial cells via V(1A) receptors and modulates mesangial cell growth not only by direct action but also through stimulation of VEGF secretion. This autocrine mechanism might contribute to glomerulosclerosis in renal diseases such as diabetic nephropathy.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan. atsuo.tahara@jp.astellas.com
authors.forename: Atsuo
authors.initials: A
authors.lastname: Tahara
authors.forename: Junko
authors.initials: J
authors.lastname: Tsukada
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tomura
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Yatsu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shibasaki
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D065092:Antidiuretic Hormone Receptor Antagonists; D019898:Autocrine Communication / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000096:biosynthesis; D006965:Hyperplasia; D006984:Hypertrophy; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D014667:Vasopressins / Q000378:metabolism / Q000494:pharmacology*
chemical_list: 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; D000906:Antibodies; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D024141:Collagen Type IV; D010880:Piperidines; D017483:Receptors, Vasopressin; D042461:Vascular Endothelial Growth Factor A; D014667:Vasopressins