EXPRESSION OF FETAL KIDNEY GROWTH-FACTORS IN A KIDNEY TUMOR LINE - ROLE OF FGF2 IN KIDNEY DEVELOPMENT

To identify growth factors which may play a role in kidney organogenes is, we have analyzed culture supernatants from the pediatric kidney tu mor cell line G401. G401 cells were found to secrete fibroblast growth factor 2 (FGF2), a potent mitogen for mesenchymal cells, OP-1/BMP7, a n epithelial cell growth inhibitor, and midkine (MK). Northern blottin g confirmed expression of FGF2, OP-1/BMP7 and MK mRNA, as well as Wnt5 A mRNA in G401 cells. In situ hybridization and immunocytochemistry on human fetal kidney demonstrated FGF2 expression in epithelial cells o f the branching ureteric bud epithelium, nephron precursors ('S-shaped bodies'), proximal tubule epithelium and the parietal epithelium of t he glomerulus. FGF2 protein in condensed 'caps' of induced mesenchymal cells was also detected by immunocytochemistry. FGF2 protein was foun d to be concentrated in nuclei, particularly in proximal tubule epithe lial cells. Recombinant FGF2 was found to act as a mitogen on primary mouse fetal kidney cell cultures. The results demonstrate G401 cells s ecrete a variety of fetal kidney growth factors and that FGF2 may act as a mitogen for fetal kidney cells and thus could play a role in the morphogenesis of the kidney.