RT Journal Article
SR Electronic
T1 Localisation of transforming growth factor β1 and β3 mRNA transcripts in normal and fibrotic human lung
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 549
OP 556
DO 10.1136/thx.56.7.549
VO 56
IS 7
A1 R K Coker
A1 G J Laurent
A1 P K Jeffery
A1 R M du Bois
A1 C M Black
A1 R J McAnulty
YR 2001
UL http://thorax.bmj.com/content/56/7/549.abstract
AB BACKGROUND Transforming growth factor β1 is implicated in the pathogenesis of lung fibrosis. It promotes extracellular matrix accumulation by increasing procollagen synthesis and reducing degradation. TGFβ1 gene and protein expression increase in experimental lung fibrosis, and TGFβ1 antibodies attenuate fibrosis in mice. The role of other TGFβ isoforms is unclear. This study aimed to localise TGFβ1 and TGFβ3 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. TGFβ1 and TGFβ3 mRNA transcripts were widespread in normal lung and localised to alveolar macrophages and bronchiolar epithelium. TGFβ1 but not TGFβ3 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. TGFβ1 gene expression was enhanced in some patients. TGFβ3 was expressed in fibrotic lung but was not consistently altered compared with controls.CONCLUSION TGFβ1mRNA transcripts were localised in normal and fibrotic human lung and TGFβ3 gene expression in human lung fibrosis was shown for the first time. The results suggest that TGFβ1 may play the predominant role in pathogenesis. It is suggested that TGFβ1 should be the primary target of anticytokine treatments for pulmonary fibrosis.