An endothelial growth factor involved in rat renal development

J Clin Invest. 1998 Sep 15;102(6):1208-19. doi: 10.1172/JCI785.


In the kidney, there is a close and intricate association between epithelial and endothelial cells, suggesting that a complex reciprocal interaction may exist between these two cell types during renal ontogeny. Thus, we examined whether metanephrogenic mesenchymal cells secrete endothelial mitogens. With an endothelial mitogenic assay and sequential chromatography of the proteins in the media conditioned by a cell line of rat metanephrogenic mesenchymal cells (7.1.1 cells), we isolated a protein whose amino acid analysis identified it as hepatoma-derived growth factor (HDGF). Media conditioned with Cos-7 cell transfected with HDGF cDNA stimulated endothelial DNA synthesis. With immunoaffinity purified antipeptide antibodies, we found that HDGF was widely distributed in the renal anlage at early stages of development but soon concentrated at sites of active morphogenesis and, except for some renal tubules, disappeared from the adult kidney. From a 7.1.1 cells cDNA library, a clone of most of the translatable region of HDGF was obtained and used to synthesize digoxigenin-labeled riboprobes. In situ hybridization showed that during kidney development mRNA for HDGF was most abundant at sites of nephron morphogenesis and in ureteric bud cells while in the adult kidney transcripts disappeared except for a small population of distal tubules. Thus, HDGF is an endothelial mitogen that is present in embryonic kidney, and its expression is synchronous with nephrogenesis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cattle
  • Culture Media, Conditioned
  • DNA, Complementary
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / immunology
  • Endothelial Growth Factors / metabolism*
  • Endothelium, Vascular / growth & development*
  • Growth Substances / genetics
  • Growth Substances / immunology
  • Growth Substances / metabolism*
  • Immunoblotting
  • Intercellular Signaling Peptides and Proteins*
  • Kidney Glomerulus / embryology*
  • Mesoderm / metabolism
  • Mitogens / genetics
  • Mitogens / immunology
  • Mitogens / metabolism*
  • Models, Biological
  • Molecular Sequence Data
  • Morphogenesis
  • Neovascularization, Physiologic*
  • Rats
  • Recombinant Proteins / metabolism
  • Tissue Distribution


  • Culture Media, Conditioned
  • DNA, Complementary
  • Endothelial Growth Factors
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Mitogens
  • Recombinant Proteins
  • hepatoma-derived growth factor