Localisation of transforming growth factor beta(1) and beta(3) mRNA transcripts in normal and fibrotic human lung

Background - Transforming growth factor p, is implicated in the pathogenesi s of lung fibrosis. It promotes extracellular matrix accumulation by increa sing procollagen synthesis and reducing degradation. TGF beta (1) gene and protein expression increase in experimental lung fibrosis, and TGF beta (1) antibodies attenuate fibrosis in mice. The role of other TGF beta isoforms is unclear. This study aimed to localise TGF beta (1) and TGF beta (2) gen e expression in fibrotic human lung and compare it with that in normal huma n lung. Methods - Lung tissue from patients with cryptogenic fibrosing alveolitis a nd fibrosis associated with systemic sclerosis was examined by in situ hybr idisation. Macroscopically normal lung from carcinoma resections was used a s control tissue. Digoxigenin labelled riboprobes were synthesised from TGF beta isoform specific cDNA templates. Results - The digoxigenin labelled riboprobes were sensitive and permitted precise cellular localisation of mRNA transcripts. TGF beta (1) and TGF bet a (3) mRNA transcripts were widespread in normal lung and localised to alve olar macrophages and bronchiolar epithelium. TGF beta (1) but not TGF beta (3) mRNA was detected in mesenchymal and endothelial cells. In fibrotic lun g tissue mRNA transcripts for both isoforms were also detected in metaplast ic type II cells. TGF beta (1) gene expression was enhanced in some patient s. TGF beta (3) was expressed in fibrotic lung but was not consistently alt ered compared with controls. Conclusion - TGF beta (1), mRNA transcripts were localised in normal and fi brotic human lung and TGF beta (3) gene expression in human lung fibrosis w as shown for the first time. The results suggest that TGF beta (1) may play the predominant role in pathogenesis. It is suggested that TGF beta (1) sh ould be the primary target of anticytokine treatments for pulmonary fibrosi s.