Fetal mouse kidney maturation in vitro: coordinated influences of epidermal growth factor, transferrin and hydrocortisone.
We have investigated the individual and combined actions of epidermal growth factor (EGF), transferrin and hydrocortisone on the maturation of whole fetal mouse metanephroi maintained in serum-free conditions for up to 5 days. The presence of EGF (100 ng/ml) resulted in elevated levels of [3H]-thymidine incorporation when compared to controls; autoradiograms showed that the proliferation of mesenchymal cells in the nephrogenic zone is particularly enhanced as verified by cell counting. Brush border hydrolase activities (alkaline phosphatase and gamma-glutamyltransferase), on the other hand, were significantly diminished. Transferrin (5 micrograms/ml) slightly stimulated DNA synthesis and potentiated EGF mitogenic action. The activation of DNA replication by the growth factor seems to be mediated through the protein kinase C pathway. When added alone, hydrocortisone (10(-6) M) strongly inhibited DNA synthesis, stimulated hydrolase activities and exerted a positive effect on brush border differentiation. When combined with EGF or to EGF + transferrin, hydrocortisone counteracted the effects of these latter peptides on DNA synthesis and enzyme activities. Considering the earlier observation of a reciprocal relation between proliferation and differentiation during the neotubulogenic phase of kidney development, the results described in the current study suggest that synergistic and synarchic actions of these heterologous factors are involved in the regulation of tubulogenesis.
Chailler
P
P
Département d'anatomie et de biologie cellulaire, Faculté de médecine, Université de Sherbrooke, Québec, Canada.
Ferrari
J
J
Brière
N
N
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D006867:Hydrolases / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects / Q000196:embryology; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D011247:Pregnancy; D014176:Protein Biosynthesis; D014168:Transferrin / Q000494:pharmacology
D014168:Transferrin; D004815:Epidermal Growth Factor; D004247:DNA; D006867:Hydrolases; D006854:Hydrocortisone