| First Author | Tibboel J | Year | 2015 |
| Journal | Am J Respir Cell Mol Biol | Volume | 52 |
| Issue | 4 | Pages | 448-58 |
| PubMed ID | 25180700 | Mgi Jnum | J:232285 |
| Mgi Id | MGI:5776442 | Doi | 10.1165/rcmb.2014-0037OC |
| Citation | Tibboel J, et al. (2015) Hypoxia-inducible factor-1 stimulates postnatal lung development but does not prevent O2-induced alveolar injury. Am J Respir Cell Mol Biol 52(4):448-58 |
| abstractText | This study investigated whether hypoxia-inducible factor (HIF)-1 influences postnatal vascularization and alveologenesis in mice and whether stable (constitutive-active) HIF could prevent hyperoxia-induced lung injury. We assessed postnatal vessel and alveolar formation in transgenic mice, expressing a stable, constitutive-active, HIF1alpha-subunit (HIF-1alphaDeltaODD) in the distal lung epithelium. In addition, we compared lung function, histology, and morphometry of neonatal transgenic and wild-type mice subjected to hyperoxia. We found that postnatal lungs of HIF-1alphaDeltaODD mice had a greater peripheral vessel density and displayed advanced alveolarization compared with control lungs. Stable HIF-1alpha expression was associated with increased postnatal expression of angiogenic factors, including vascular endothelial growth factor, angiopoietins 1 and 2, Tie2, and Ephrin B2 and B4. Hyperoxia-exposed neonatal HIF-1alphaDeltaODD mice exhibited worse lung function but had similar histological and surfactant abnormalities compared with hyperoxia-exposed wild-type controls. In conclusion, expression of constitutive-active HIF-1alpha in the lung epithelium was associated with increased postnatal vessel growth via up-regulation of angiogenic factors. The increase in postnatal vasculature was accompanied by enhanced alveolar formation. However, stable HIF-1alpha expression in the distal lung did not prevent hyperoxia-induced lung injury in neonates but instead worsened lung function. |
