Tohoku J. Exp. Med., 2001, 195 (1)

Glomerular Endothelial Cells Are Maintained by Vascular Endothelial Growth Factor in the Adult Kidney

YASUNORI KITAMOTO, MOTOHIRO TAKEYA¹, HIROSHI TOKUNAGA and KIMIO TOMITA

The Third Department of Internal Medicine, and ¹Second Department of Pathology,Kumamoto University School of Medicine, Kumamoto 860-8556

Vascular endothelial growth factor (VEGF) is known to maintain endothelial cells of immature vessels and is constitutively expressed in the kidney from the embryo to adult. We tested the hypothesis that VEGF activity is needed to maintain glomerular endothelial cells in the adult. Neutralizing antibody to VEGF165 was intraperitoneally administered to mice for 3 days to strongly suppress its intrinsic activity. On the fourth day, mice were sacrificed and tissues were examined by light and electron microscopies. Vascular casts of renal vessels were observed by a scanning electron microscopy. Distribution of the administered antibody and expressions of VEGF and Flk-1 were examined immunohistochemically. The suppression of endogenous VEGF activity caused swelling and vacuolation of endothelial cells and obstruction of capillaries in the glomerulus. Other tissues were not impaired significantly. The administered antibody was specifically localized to the glomerulus, and was found more predominantly in the juxta-medullary than in the cortical glomerulus. This pattern of antibody deposition was similar to that of Flk-1. VEGF expression in the glomerulus was compensatively elevated by the antibody treatment. These results show that demand for VEGF signaling in the glomerulus is much higher than in other tissues, probably to protect its endothelial cells against high tension for blood filtration. This demand may be fulfilled by enriched signaling through the Flk-1 in the glomerulus.

Keywords —— developed kidney; endogenous VEGF; neutralizing antibody; glomerular structure; Flk-1

© 2001 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2001, 195, 43-54

Address for reprints: Dr. Yasunori Kitamoto, The Third Department of Internal Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-8556, Japan.

e-mail: yasunori@kaiju.medic.kumamoto-u.ac.jp