Disrupted postnatal lung development in heme oxygenase-1 deficient mice.
Publication/Presentation Date
10-10-2010
Abstract
BACKGROUND: Heme oxygenase (HO) degrades cellular heme to carbon monoxide, iron and biliverdin. The HO-1 isoform is both inducible and cyto-protective during oxidative stress, inflammation and lung injury. However, little is known about its precise role and function in lung development. We hypothesized that HO-1 is required for mouse postnatal lung alveolar development and that vascular expression of HO-1 is essential and protective during postnatal alveolar development.
METHODS: Neonatal lung development in wildtype and HO-1 mutant mice was evaluated by histological and molecular methods. Furthermore, these newborn mice were treated with postnatal dexamethasone (Dex) till postnatal 14 days, and evaluated for lung development.
RESULTS: Compared to wildtype littermates, HO-1 mutant mice exhibited disrupted lung alveolar structure including simplification, disorganization and reduced secondary crest formation. These defects in alveolar development were more pronounced when these mice were challenged with Dex treatment. Expression levels of both vascular endothelial and alveolar epithelial markers were also further decreased in HO-1 mutants after Dex treatment.
CONCLUSIONS: These experiments demonstrate that HO-1 is required in normal lung development and that HO-1 disruption and dexamethasone exposure are additive in the disruption of postnatal lung growth. We speculate that HO-1 is involved in postnatal lung development through modulation of pulmonary vascular development.
Volume
11
Issue
1
First Page
142
Last Page
142
ISSN
1465-993X
Published In/Presented At
Zhuang, T., Zhang, M., Zhang, H., Dennery, P. A., & Lin, Q. S. (2010). Disrupted postnatal lung development in heme oxygenase-1 deficient mice. Respiratory research, 11(1), 142. https://doi.org/10.1186/1465-9921-11-142
Disciplines
Medicine and Health Sciences
PubMedID
20932343
Department(s)
Fellows and Residents
Document Type
Article