Growth factor control of growth and epithelial differentiation in embryonic lungs.

embryonic lung cultures were exposed to either EGF (10 ng/ml) or TGF beta 1 (2 ng/ml) for 72 h, and branching morphogenesis, cell proliferation, and epithelial differentiation (the expression of DSPC synthesis and of surfactant protein C (SP-C) mRNA) were studied. EGF treatment stimulated branching morphogenesis (measured as the number of terminal left lung buds), epithelial differentiation, and cell proliferation. Branching morphogenesis was increased compared to controls after 48 h of culture by 47% and after 72 h by 34% (P < 0.0005). Choline incorporation into DSPC was stimulated by 343% (P = 0.05). SP-C expression was increased sixfold. Thymidine incorporation was stimulated by 49% (P < 0.05). The effects of EGF on thymidine labeling were distributed among epithelial cells of the airway walls and of the branching tips, and also the mesenchyme (P < 0.01 for each area compared to controls). In contrast, TGF beta 1 did not alter the number of terminal left lung buds, inhibited choline incorporation into DSPC by 35% (P < 0.05), and had no effect on thymidine incorporation (87% of control). There was increased thymidine labeling at the branching tips (P < 0.01), while other areas were not different from controls. We conclude that both EGF and TGF beta 1 affect the development of branching morphogenesis and of epithelial differentiation in the embryonic lung.