Vascular Endothelial Growth Factor Is an Essential Molecule for Mouse Kidney Development: Glomerulogenesis and Nephrogenesis

J Clin Invest. 1997 May 15;99(10):2351-7. doi: 10.1172/JCI119416.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies
  • Basement Membrane / physiology
  • Basement Membrane / ultrastructure
  • Capillaries / embryology
  • Capillaries / physiology
  • Embryo, Mammalian
  • Embryonic and Fetal Development*
  • Endothelial Growth Factors / biosynthesis*
  • Endothelial Growth Factors / metabolism
  • Endothelial Growth Factors / physiology
  • Immunohistochemistry
  • Kidney / blood supply
  • Kidney / embryology*
  • Kidney / metabolism
  • Kidney Cortex / blood supply
  • Kidney Cortex / embryology
  • Kidney Glomerulus / embryology*
  • Kidney Glomerulus / ultrastructure
  • Lymphokines / biosynthesis*
  • Lymphokines / metabolism
  • Lymphokines / physiology
  • Mice
  • Microscopy, Electron
  • Nephrons / embryology*
  • Organ Culture Techniques
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Antibodies
  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors