Role of growth factors in molecular pathogenetic mechanism of radiation pulmonary fibrosis

Objective To investigate the role of growth factors and their receptors in radiation pulmonary fibrosis(RPF). Methods Immunohistochemisty,immunocytochemistry and in situ hybridization were used. Results The normal rat lung tissue weakly expressed TGFβ1 and TGFβ receptor (TGFβR).The expression of TGFβ1 in rat lung increased at 2 weeks after irradiation and its highest level maintained from 8 weeks to 3 months.The positive localization of TGFβ1 in lung was the epithelial cells of bronchi,alveolar macrophages,alveolar epithelial cells, smooth muscle cells of the bronchial and arteriolar wall and fibroblasts.The expression of TGFβ2 was similar to that of TGFβ1.The time of increased expression of TGFβR was later than that of TGFβ1.i,e. It increased at 8 weeks and kept a higher level of expression throughout one year.Stronger expressions of the bFGF and PDGF were also observed in 2-3 months postirradiation.The expression of TGFβ1 in the cells of bronchoalveolar lavage fluid was investigated.The results showed that macrophages were one of the earliest cells showing positive reaction,i,e. they presented positive at 1 week. For the cultured Wistar rat lung fibroblasts,TGFβ1 expression was stronger at 3 months postirradiation. By means of in situ hybridization with TGFβ1 probe and α1(I) oligonucleotide probe,the expression of TGFβ1 mRNA was increased at 2-8 weeks and α1(I) procollagen mRAN was increased at 6 weeks, but the expression peak appeared at 3 months postirradiation. The expressions of TGFβ1 and α1(I) procollagen were mutually connected and overlapped both in time and space. Conclusion TGFβ1 may play an important role in the pathogenesis of RPF. TGFβ2,TGFβR,bFGF and PDGF-A also participate in the pathogenetic process.