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Medical Research Council Centre for Developmental Neurobiology, King's College London, London, UK
CORRESPONDENCE: M. Maden, MRC Centre for Developmental Neurobiology, 4th floor New Hunt's House, King's College London, Guy's Campus, London Bridge, London, SE1 1UL, UK. Fax: 44 2078486798. E-mail: malcolm.maden@kcl.ac.uk
Keywords: alveolar regeneration, dexamethasone, lung, mouse, regeneration, retinoic acid
Received: December 19, 2002
Accepted August 14, 2003
This work was funded by The Wellcome Trust via a Wellcome Trust Research Training Fellowship to M. Hind.
Recent data suggests that exogenous retinoic acid (RA) can induce alveolar regeneration in a mouse and a rat model of experimental emphysema and disrupted alveolar development. This may be because RA is required during normal alveolar development and the subsequent provision of RA reawakens the gene cascades used during development.
Here, additional evidence that RA is required during alveologenesis in the mouse is provided by showing that disulphiram disrupts this process. A further model of disrupted alveolar development using dexamethasone administered postnatally is then described, and it is further shown that RA administered to these adult mice restores the lung architecture to normal.
Alveolar regeneration with retinoic acid may therefore be an important novel therapeutic approach to the treatment of respiratory diseases characterised by a reduced gas-exchanging surface area, such as bronchopulmonary dysplasia and emphysema.
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