Ontogeny and localization of TGF-β type I receptor expression during lung development

Transforming growth factor (TGF)-β is a family of multifunctional cytokines controlling cell growth, differentiation, and extracellular matrix deposition in the lung. The biological effects of TGF-β are mediated by type I (TβR-I) and II (TβR-II) receptors. Our previous studies show that the expression of TβR-II is highly regulated in a spatial and temporal fashion during lung development. In the present studies, we investigated the temporal-spatial pattern and cellular expression of TβR-I during lung development. The expression level of TβR-I mRNA in rat lung at different embryonic and postnatal stages was analyzed by Northern blotting. TβR-I mRNA was expressed in fetal rat lungs in early development and then decreased as development proceeded. The localization of TβR-I in fetal and postnatal rat lung tissues was investigated by using in situ hybridization performed with an antisense RNA probe. TβR-I mRNA was present in the mesenchyme and epithelium of gestational day 14 rat lungs. An intense TβR-I signal was observed in the epithelial lining of the developing bronchi. In gestational day 16 lungs, the expression of TβR-I mRNA was increased in the mesenchymal tissue. The epithelium in both the distal and proximal bronchioles showed a similar level of TβR-I expression. In postnatal lungs, TβR-I mRNA was detected in parenchymal tissues and blood vessels. We further studied the expression of TβR-I in cultured rat lung cells. TβR-I was expressed by cultured rat lung fibroblasts, microvascular endothelial cells, and alveolar epithelial cells. These studies demonstrate a differential regulation and localization of TβR-I that is different from that of TβR-II during lung development. TβR-I, TβR-II, and TGF-β isoforms exhibit distinct but overlapping patterns of expression during lung development. This implies a distinct role for TβR-I in mediating TGF-β signal transduction during lung development.