AN ENDOTHELIAL GROWTH-FACTOR INVOLVED IN RAT RENAL DEVELOPMENT

In the kidney, there is a close and intricate association between epit helial and endothelial cells, suggesting that a complex reciprocal int eraction may exist between these two cell types during renal ontogeny. Thus, we examined whether metanephrogenic mesenchymal cells secrete e ndothelial mitogens. With an endothelial mitogenic assay and sequentia l chromatography of the proteins in the media conditioned by a cell li ne 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 w ith HDGF cDNA stimulated endothelial DNA synthesis. With immunoaffinit y purified antipeptide antibodies, we found that HDGF was widely distr ibuted in the renal anlage at early stages of development but soon con centrated at sites of active morphogenesis and, except for some renal tubules, disappeared from the adult kidney. From a 7.1.1 cells cDNA li brary, a clone of most of the translatable region of HDGF was obtained and used to synthesize digoxigen-inlabeled riboprobes. In situ hybrid ization showed that during kidney development mRNA for HDGF was most a bundant at sites of nephron morphogenesis and in ureteric bud cells wh ile in the adult kidney transcripts disappeared except for a small pop ulation of distal tubules. Thus, HDGF is an endothelial mitogen that i s present in embryonic kidney, and its expression is synchronous with nephrogenesis.