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

Coker, RK; Laurent, GJ; Jeffery, PK; du Bois, RM; Black, CM; McAnulty, RJ; (2001) Localisation of transforming growth factor beta(1) and beta(3) mRNA transcripts in normal and fibrotic human lung. Thorax , 56 (7) 549 - 556. 10.1136/thorax.56.7.549 .

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Abstract

Background - Transforming growth factor p, is implicated in the pathogenesis of lung fibrosis. It promotes extracellular matrix accumulation by increasing 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) 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 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 beta (3) mRNA transcripts were widespread in normal lung and localised to alveolar macrophages and bronchiolar epithelium. TGF beta (1) but not TGF beta (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. TGF beta (1) gene expression was enhanced in some patients. TGF beta (3) was expressed in fibrotic lung but was not consistently altered compared with controls.Conclusion - TGF beta (1), mRNA transcripts were localised in normal and fibrotic human lung and TGF beta (3) gene expression in human lung fibrosis was 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) should be the primary target of anticytokine treatments for pulmonary fibrosis.

Type: Article
Title: Localisation of transforming growth factor beta(1) and beta(3) mRNA transcripts in normal and fibrotic human lung
DOI: 10.1136/thorax.56.7.549
Publisher version: http://dx.doi.org/10.1136/thorax.56.7.549
Language: English
Keywords: pulmonary fibrosis, transforming growth factor beta, gene expression, CRYPTOGENIC FIBROSING ALVEOLITIS, PULMONARY FIBROSIS, GENE-EXPRESSION, IMMUNOHISTOCHEMICAL LOCALIZATION, SYSTEMIC-SCLEROSIS, EPITHELIAL-CELLS, MURINE LUNG, IN-VITRO, MATRIX, FACTOR-BETA(1)
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
URI: http://discovery.ucl.ac.uk/id/eprint/175489
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