Deferoxamine Improves Alveolar and Pulmonary Vascular Development by Upregulating Hypoxia-inducible Factor-1 alpha in a Rat Model of Bronchopulmonary Dysplasiaopen access
- Authors
- Choi, Chang Won; Lee, Juyoung; Lee, Hyun Ju; Park, Hyoung-Sook; Chun, Yang-Sook; Kim, Beyong Il
- Issue Date
- Sep-2015
- Publisher
- KOREAN ACAD MEDICAL SCIENCES
- Keywords
- Alveolarization; Bronchopulmonary Dysplasia; Deferoxamine; Hypoxia-Inducible Factor
- Citation
- JOURNAL OF KOREAN MEDICAL SCIENCE, v.30, no.9, pp.1295 - 1301
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- JOURNAL OF KOREAN MEDICAL SCIENCE
- Volume
- 30
- Number
- 9
- Start Page
- 1295
- End Page
- 1301
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/156452
- DOI
- 10.3346/jkms.2015.30.9.1295
- ISSN
- 1011-8934
- Abstract
- Fetal lung development normally occurs in a hypoxic environment. Hypoxia-inducible factor (HIF)-1 alpha is robustly induced under hypoxia and transactivates many genes that are essential for fetal development. Most preterm infants are prematurely exposed to hyperoxia, which can halt hypoxia-driven lung maturation. We were to investigate whether the HIF-1 alpha inducer, deferoxamine (DFX) can improve alveolarization in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was produced by intra-amniotic lipopolysaccharide (LPS) administration and postnatal hyperoxia (85% for 7 days), and DFX (150 mg/kg/d) or vehicle was administered to rat pups intraperitoneally for 14 days. On day 14, the rat pups were sacrificed and their lungs were removed and examined. A parallel in vitro study was performed with a human small airway epithelial cell line to test whether DFX induces the expression of HIF-1 alpha and its target genes. Alveolarization and pulmonary vascular development were impaired in rats with BPD. However, DFX significantly ameliorated these effects. Immunohistochemical analysis showed that HIF-1 alpha was significantly upregulated in the lungs of BPD rats treated with DFX. DFX was also found to induce HIF-1 alpha in human small airway epithelial cells and to promote the expression of HIF-1 alpha target genes. Our data suggest that DFX induces and activates HIF-1 alpha, thereby improving alveolarization and vascular distribution in the lungs of rats with BPD.
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