Thorax 2001;56:549-556 ( July )

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

R K Coker^a, G J Laurent^a, P K Jeffery^b, R M du Bois^b, C M Black^c, R J McAnulty^a

^a Centre for Cardiopulmonary Biochemistry & Respiratory Medicine, Royal Free & University College Medical School, University College London, Rayne Institute, London WC1E 6JJ, UK, ^b Respiratory Medicine, Royal Brompton National Heart & Lung Hospital, London SW3 6LY, UK, ^c Department of Rheumatology, Royal Free Hospital, London NW3 2QG, UK

Correspondence to: Dr R K Coker, Department of Respiratory Medicine, Hammersmith Hospital, Du Cane Road, London W12 OHS, UK robina.coker{at}ic.ac.uk

Received 15 September 2000; Returned to authors 20 November 2000; Revised version received 29 January 2001; Accepted for publication 26 February 2001

BACKGROUNDTransforming growth factor ₁ is implicated in the pathogenesis of lung fibrosis. It promotes extracellular matrix accumulation by increasing procollagen synthesis and reducing degradation. TGF₁ gene and protein expression increase in experimental lung fibrosis, and TGF₁ antibodies attenuate fibrosis in mice. The role of other TGF isoforms is unclear. This study aimed to localise TGF₁ and TGF₃ gene expression in fibrotic human lung and compare it with that in normal human lung.
METHODSLung 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 isoform specific cDNA templates.
RESULTSThe digoxigenin labelled riboprobes were sensitive and permitted precise cellular localisation of mRNA transcripts. TGF₁ and TGF₃ mRNA transcripts were widespread in normal lung and localised to alveolar macrophages and bronchiolar epithelium. TGF₁ but not TGF₃ 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. TGF₁ gene expression was enhanced in some patients. TGF₃ was expressed in fibrotic lung but was not consistently altered compared with controls.
CONCLUSIONTGF₁ mRNA transcripts were localised in normal and fibrotic human lung and TGF₃ gene expression in human lung fibrosis was shown for the first time. The results suggest that TGF₁ may play the predominant role in pathogenesis. It is suggested that TGF₁ should be the primary target of anticytokine treatments for pulmonary fibrosis.


Keywords: pulmonary fibrosis; transforming growth factor ; gene expression

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© 2001 by Thorax
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