Localisation of transforming growth factor beta1 and beta3 mRNA transcripts in normal and fibrotic human lung

BACKGROUND: Transforming growth factor beta1 is implicated in the pathogenesis of lung fibrosis. It promotes extracellular matrix accumulation by increasing procollagen synthesis and reducing degradation. TGFbeta1 gene and protein expression increase in experimental lung fibrosis, and TGFbeta1 antibodies attenuate fibrosis in mice. The role of other TGFbeta isoforms is unclear. This study aimed to localise TGFbeta1 and TGFbeta3 gene expression in fibrotic human lung and compare it with that in normal human lung. METHODS: Lung tissue from patients with cryptogenic fibrosing alveolitis and fibrosis associated with systemic sclerosis was examined by in situ hybridisation. Macroscopically normal lung from carcinoma resections was used as control tissue. Digoxigenin labelled riboprobes were synthesised from TGFbeta isoform specific cDNA templates. RESULTS: The digoxigenin labelled riboprobes were sensitive and permitted precise cellular localisation of mRNA transcripts. TGFbeta1 and TGFbeta3 mRNA transcripts were widespread in normal lung and localised to alveolar macrophages and bronchiolar epithelium. TGFbeta1 but not TGFbeta3 mRNA was detected in mesenchymal and endothelial cells. In fibrotic lung tissue mRNA transcripts for both isoforms were also detected in metaplastic type II cells. TGFbeta1 gene expression was enhanced in some patients. TGFbeta3 was expressed in fibrotic lung but was not consistently altered compared with controls. CONCLUSION: TGFbeta1 mRNA transcripts were localised in normal and fibrotic human lung and TGFbeta3 gene expression in human lung fibrosis was shown for the first time. The results suggest that TGFbeta1 may play the predominant role in pathogenesis. It is suggested that TGFbeta1 should be the primary target of anticytokine treatments for pulmonary fibrosis.