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

Transforming growth factor (TGF)-beta is a family of multifunctional cytoki nes controlling cell growth, differentiation, and extracellular matrix depo sition in the lung. The biological effects of TGF-beta are mediated by type I (T beta R-I) and II (T beta R-II) receptors. Our previous studies show t hat the expression of T beta R-II is highly regulated in a spatial and temp oral fashion during lung development. In the present studies, we investigat ed the temporal-spatial pattern and cellular expression of T beta R-I durin g lung development. The expression level of T beta R-I mRNA in rat lung at different embryonic and postnatal stages was analyzed by Northern blotting. T beta R-I mRNA was expressed in fetal rat lungs in early development and then decreased as development proceeded. The localization of T beta R-I in fetal and postnatal rat lung tissues was investigated by using in situ hybr idization performed with an antisense RNA probe. T beta R-I mRNA was presen t in the mesenchyme and epithelium of gestational day 14 rat lungs. An inte nse T beta R-I signal was observed in the epithelial lining of the developi ng bronchi. In gestational day 16 lungs, the expression of T beta R-I mRNA was increased in the mesenchymal tissue. The epithelium in both the distal and proximal bronchioles showed a similar level of T beta R-I expression. I n postnatal lungs, T beta R-I mRNA was detected in parenchymal tissues and blood vessels. We further studied the expression of T beta R-I in cultured rat lung cells. T beta R-I was expressed by cultured rat lung fibroblasts, microvascular endothelial cells, and alveolar epithelial cells. These studi es demonstrate a differential regulation and localization of T beta R-I tha t is different from that of T beta R-II during lung development. T beta R-I , T beta R-II, and TGF-beta isoforms exhibit distinct but overlapping patte rns of expression during lung development. This implies a distinct role for T beta R-I in mediating TGF-beta signal transduction during lung developme nt.