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• W4234479124 abstract "BACKGROUND Transforming growth factor β 1 is implicated in the pathogenesis of lung fibrosis. It promotes extracellular matrix accumulation by increasing procollagen synthesis and reducing degradation. TGFβ 1 gene and protein expression increase in experimental lung fibrosis, and TGFβ 1 antibodies attenuate fibrosis in mice. The role of other TGFβ isoforms is unclear. This study aimed to localise TGFβ 1 and TGFβ 3 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 TGFβ isoform specific cDNA templates. RESULTS The digoxigenin labelled riboprobes were sensitive and permitted precise cellular localisation of mRNA transcripts. TGFβ 1 and TGFβ 3 mRNA transcripts were widespread in normal lung and localised to alveolar macrophages and bronchiolar epithelium. TGFβ 1 but not TGFβ 3 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. TGFβ 1 gene expression was enhanced in some patients. TGFβ 3 was expressed in fibrotic lung but was not consistently altered compared with controls. CONCLUSION TGFβ 1 mRNA transcripts were localised in normal and fibrotic human lung and TGFβ 3 gene expression in human lung fibrosis was shown for the first time. The results suggest that TGFβ 1 may play the predominant role in pathogenesis. It is suggested that TGFβ 1 should be the primary target of anticytokine treatments for pulmonary fibrosis." @default.
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• W4234479124 date "2001-07-01" @default.
• W4234479124 modified "2023-09-26" @default.
• W4234479124 title "Localisation of transforming growth factor β1 and β3 mRNA transcripts in normal and fibrotic human lung" @default.
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• W4234479124 doi "https://doi.org/10.1136/thx.56.7.549" @default.
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