Deferoxamine Improves Alveolar and Pulmonary Vascular Development by Upregulating Hypoxia-inducible Factor-1α in a Rat Model of Bronchopulmonary Dysplasia

Journal of Korean Medical Science
Chang Won ChoiBeyong Il Kim

Abstract

Fetal lung development normally occurs in a hypoxic environment. Hypoxia-inducible factor (HIF)-1α 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-1α 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-1α 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-1α was significantly upregulated in the lungs of BPD rats treated with DFX. DFX was also found to induce HIF-1α in human small airway ...Continue Reading

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Citations

Jun 1, 2016·Frontiers in Medicine·Cristina M Alvira
Aug 19, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Cristian CoarfaKrithika Lingappan
Oct 4, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·David E Surate SolaligueRory E Morty
Sep 27, 2019·Journal of the American Society of Nephrology : JASN·Shreyak Sharma, David E Leaf
Jun 20, 2020·American Journal of Respiratory and Critical Care Medicine·Kellen HirschSteven H Abman
Nov 17, 2017·The Journal of Pediatrics·Cristina M Alvira, Rory E Morty

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Methods Mentioned

BETA
transfection
PCR

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