Kitamoto Y, Tokunaga H, Tomita K
Third Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto 860, Japan.
J Clin Invest. 1997 May 15;99(10):2351-7. doi: 10.1172/JCI119416.
Homeostasis of body fluid is maintained by the kidneys, which contain two million glomeruli for blood filtration. A glomerulus is formed by growth of Bowman's capsule harmonized with a capillary during kidney development. The vascular endothelial growth factor (VEGF) is an essential angiogenic cytokine, and VEGF deficiency is known to be fatal in mice in early embryonic stages. As secretions of VEGF from cultured kidneys vary according to developmental stages, the role of VEGF in kidney development was studied in vivo by blocking the endogenous VEGF activity with antibody in newborn mice, in which most organs are already developed but kidneys are still developing. The antibody-treated animals showed normal growth but systemic edema. Vessel formation in the superficial renal cortex was disturbed, nephrogenic areas were diminished, and the number of developing nephrons decreased significantly. Many abnormal glomeruli, lacking capillary tufts, were observed in the antibody-treated mice, and VEGF expression in their Bowman's capsule showed a compensatory increase. These results suggest that VEGF mediates communication between the Bowman's capsule and capillary endothelial cells for developing a glomerulus as well as promoting nephrogenesis. In conclusion, VEGF is likely to be an essential molecule for kidney development, and especially for glomerulogenesis.
体液平衡由肾脏维持,肾脏包含两百万个用于血液过滤的肾小球。肾小球是在肾脏发育过程中由鲍曼囊与毛细血管协调生长形成的。血管内皮生长因子(VEGF)是一种重要的血管生成细胞因子,已知VEGF缺乏在小鼠胚胎早期是致命的。由于培养的肾脏中VEGF的分泌随发育阶段而变化,因此通过在新生小鼠中用抗体阻断内源性VEGF活性来体内研究VEGF在肾脏发育中的作用,新生小鼠中大多数器官已经发育,但肾脏仍在发育。经抗体处理的动物生长正常,但出现全身性水肿。浅表肾皮质中的血管形成受到干扰,肾发生区域减少,发育中的肾单位数量显著减少。在经抗体处理的小鼠中观察到许多缺乏毛细血管丛的异常肾小球,并且它们鲍曼囊中VEGF的表达出现代偿性增加。这些结果表明,VEGF介导鲍曼囊与毛细血管内皮细胞之间的通讯以形成肾小球,并促进肾发生。总之,VEGF可能是肾脏发育尤其是肾小球发生的必需分子。