Growth Factor Control of Growth and Epithelial Differentiation in Embryonic Lungs

Abstract

Branching morphogenesis and epithelial differentiation occur simultaneously during lung development, hence controlling factors may affect both aspects of development simultaneously. We hypothesized that in the embryonic lung EGF and TGFβ1 alter both epithelial differentiation and developmental morphogenesis. Day 10$\text{1}\text{2}$embryonic lung cultures were exposed to either EGF (10 ng/ml) or TGFβ1 (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, TGFβ1 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 TGFβ1 affect the development of branching morphogenesis and of epithelial differentiation in the embryonic lung.