Transforming growth factor beta2, but not beta1 and beta3, is critical for early rat lung branching

Mesenchymal-epithelial tissue interactions are critical for lung branching morphogenesis, and polypeptide growth factors are likely involved in these tissue interactions. Transforming growth factorbetas (TGFbetas) have been implicated in lung development, but their involvement in early lung branching morphogenesis is unclear. In the present study, we investigated the role of the three mammalian TGFbeta subtypes (beta1, beta2, and beta3) and their receptors (type III (TbetaR-III), type II (TbetaR-II), and two types I (TbetaR-I), ALK-1 and ALK-5) in early rat lung organogenesis by using an embryonic rat lung explant culture. Transcripts and proteins for all three TGFbetas and their receptors were detected during the embryonic period of fetal rat lung development. Inhibition of TGFbeta2, but not beta1 and beta3, with antisense oligonucleotides and neutralizing antibodies resulted in significant inhibition of early lung branching in culture. Addition of minute amounts (