Evaluation of heparin-binding growth factors in rescuing morphogenesis of heparitinase-treated mouse embryonic lung...

In vitro development of embryonic mouse lung explants was hindered by digestion with heparitinase, which removed about 40% of [35S] sulfate-labeled heparan sulfate synthesized. The enzyme-treated explants were inhibited in branching morphogenesis and the mesenchymal tissue was thin. Addition of basic fibroblast growth factor (bFGF), a typical heparin-binding growth factor, restored the inhibition caused by heparitinase in branching morphogenesis. Addition of midkine (MK), another heparin-binding growth factor, showed a weak effect on branching morphogenesis, but exhibited an effect in restoring development of mesenchymal tissue. These data together with the distribution of the factors indicate that both are involved in development of the lung. Heparitinase-treated explants can be useful models for evaluating roles played by various heparin-binding growth factors.