Epithelial-mesenchymal interactions and lung branching morphogenesis. Roleof polyamines and transforming growth factor beta(1)

Lung branching morphogenesis is a result of epithelial-mesenchymal interact ions, which are in turn dependent on extracellular matrix composition and c ytokine regulation. Polyamines have recently been demonstrated as able to m odify chick embryo skin differentiation. In this work we have examined the effects of putrescine and spermidine during chick embryo lung morphogenesis in organotypic cultures by morphological, histochemical and biochemical ex amination. To verify the role of polyamines, we used specific inhibitors, s uch as bis-cyclohexylammonium sulphate and alfa-difluoromethylornithine, an d transforming growth factor beta (1), an ornithine decarboxylase and polya mine stimulator. Our data show that lung morphogenesis is significantly alt ered following the induced mesenchymal glycosaminoglycan changes. The incre ase of mesenchymal glycosaminoglycans is correlated with a stimulation of l ung development in the presence of polyamines, and with its inhibition when transforming growth factor beta (1), is added to the culture medium. The m orphometric data show a uniform increase of both the mesenchyme and epithel ial branching with spermidine and putrescine stimulus, whereas the mesenchy mal substance alone is significantly increased in apical-median lung sectio ns with transforming growth factor beta (1), and transforming growth factor beta (1) + spermidine lung cultures. Transforming growth factor beta (1) a nd transforming growth factor beta (1) + spermidine confirm the blocking of epithelial branching formations and fibroblast activation, and show that p olyamines are unable to prevent the blocking of epithelial cells due to the inhibitory effect of transforming growth factor beta (1).