Vasopressin regulates rat mesangial cell growth by inducing autocrine secretion of vascular endothelial growth factor |
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Authors: | Atsuo Tahara Junko Tsukada Yuichi Tomura Takeyuki Yatsu Masayuki Shibasaki |
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Institution: | (1) Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba Ibaraki, 305-8585, Japan |
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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 V1A receptor-selective antagonist, confirming this is a V1A 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 V1A receptor-selective antagonist and partially abolished by the anti-VEGF antibody. These results indicate that AVP increases
VEGF secretion in rat mesangial cells via V1A 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. |
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