EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA RECEPTORS DURING HYPEROXIA-INDUCED LUNG INJURY AND REPAIR

Lung injury and repair processes involve many cellular activities. inc luding cell growth, differentiation, and remodeling of extracellular m atrix components. Transforming growth factor-beta (TGF-beta) is a majo r class of signaling peptide growth factors regulating these cellular activities. Type I (T beta RI) and type II (T beta RII) receptors for TGF-beta are transmembrane serine/threonine kinases that are essential for TGF-beta signaling. To gain insight into the possible molecular m echanisms of lung injury and repair, we investigated the expression of T beta RI and T beta RII in an acute hyperoxia-induced model of lung injury and repair. Localization of message expression of T beta RI and T beta RII in oxygen-exposed rat lung tissue was analyzed by using in situ hybridization. T beta RI mRNA expression was found in the inters titium, capillaries, and the alveolar septa of rat lungs exposed for 6 0 h to 100% oxygen. The distribution of T beta RII mRNA in oxygen-expo sed rat lung tissue overlapped the localization of T beta RI mRNA. Tem poral changes of T beta RI and T beta RII mRNA expressions in rat lung during hyperoxic exposure and repair were examined by Northern analys is. We found that expression of T beta RI was upregulated in adult rat s undergoing prolonged exposure to 100% oxygen, and the increase of T beta RI expression persisted during 2 wk of repair of lung injury. The pattern of T beta RII expression during hyperoxic exposure and repair was distinct from that of T beta RI. The expression of T beta RII inc reased with a peak at 3 days postexposure and then declined after 7 da ys of repair. Changes of T beta RI and T beta RII protein expressions in rat lung during hyperoxic exposure and repair were examined further by Western blot analysis, which correlated with the mRNA expression. The results suggest that T beta RI and T beta RII may play important r oles during the lung injury and repair by mediating signaling activity of TGF-beta and may regulate interactions between the mesenchyme and the epithelium.