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Retinoids Have Differing Efficacies on Alveolar Regeneration in a Dexamethasone-Treated Mouse

MRC Centre for Developmental Neurobiology, King's College London, London, United Kingdom

Correspondence and requests for reprints should be addressed to Professor Malcolm Maden, MRC Centre for Developmental Neurobiology, 4th floor, New Hunt's House, King's College London, Guy's Campus, London Bridge, London SE1 1UL, United Kingdom. E-mail: malcolm.maden{at}kcl.ac.uk

We have investigated the relative efficacy of a range of natural and synthetic retinoids on the induction of alveolar regeneration in a dexamethasone-treated mouse model. The aim was to explore the roles of the different retinoic acid receptors using receptor-selective agonists and to determine whether other natural retinoids in addition to all-trans-retinoic acid (tRA) were effective. Dexamethasone treatment of newborn pups led to a reduced lung surface area and increased mean chord length. Subsequently, tRA induced alveolar repair, improved mean chord length, and improved the lung surface area to volume ratio. We found that 4-oxo-RA and a retinoic acid receptor (RAR) -selective compound were as effective as tRA at inducing alveolar regeneration, with neither showing a significantly better efficacy. An RAR-selective compound was also effective, whereas a RAR-selective compound was not. Other retinoids, such as 9-cis-RA, 13-cis-RA, retinol, and a pan retinoid X receptor (RXR) agonist, do not induce significant responses. Neither did granulocyte colony-stimulating factor. We also showed that an RAR-null mutant mouse line responded to dexamethasone by failing to develop alveoli appropriately and that tRA induced alveolar regeneration, suggesting that RAR was not required for the regenerative response.

Key Words: alveolar regeneration • alveoli • dexamethasone • mouse • RAR • retinoic acid • retinoids

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