Reduction of bleomycin induced lung fibrosis by transforming growth factor β soluble receptor in hamsters
- Qingjian Wanga,
- Yinjin Wanga,
- Dallas M Hydeb,
- Philip J Gotwalsc,
- Victor E Kotelianskyc,
- Sarah T Ryanc,
- Shri N Giria
- aDepartment of Molecular Biosciences, bDepartment of Anatomy, Physiology, and Cell Biology, cSchool of Veterinary Medicine, University of California, Davis, California 95616, USA Biogen Inc, Cambridge, Massachusetts 02142, USA
- Dr S N Giri.
- Received 1 February 1999
- Revision requested 29 March 1999
- Revised 4 May 1999
- Accepted 21 May 1999
Abstract
BACKGROUND Transforming growth factor β (TGF-β) is a key mediator of collagen synthesis in the development of lung fibrosis. It has previously been shown that the administration of TGF-β antibody and TGF-β binding proteoglycan, decorin, reduced bleomycin (BL) induced lung fibrosis in animals. The present study was carried out to investigate whether intratracheal instillation of TGF-β soluble receptor (TR) would minimise the BL induced lung fibrosis in hamsters.
METHODS The effect of a recombinant TR (TGFβRII) on the lung collagen accumulation was evaluated in a BL hamster model of pulmonary fibrosis. Animals were divided into four groups and intratracheally injected with saline or BL at 6.5 U/4 ml/kg followed by intratracheal instillation of phosphate buffered saline (PBS) or 4 nmol TR in 0.3 ml twice a week. Twenty days after the first intratracheal instillation the hamsters were killed for bronchoalveolar lavage (BAL) fluid, biochemical, and histopathological analyses.
RESULTS Treatment of hamsters with TR after intratracheal instillation of BL significantly reduced BL induced lung fibrosis as shown by decreases in the lung hydroxyproline level and prolyl hydroxylase activity, although they were still significantly higher than those of the saline control. Histopathological examination showed a considerable decrease in BL induced fibrotic lesions by TR treatment. However, TR did not prevent the BL induced increases in total cells and protein in the BAL fluid.
CONCLUSIONS These results suggest that TR has antifibrotic potential in vivo and may be useful in the treatment of fibrotic diseases where increased TGF-β is associated with excess collagen accumulation.
