Deterioration of alveolar development in mice with both HIF-3α knockout and HIF-2α knockdown

• Published in: BMC research notes 2018-07, Vol.11 (1), p.449-449, Article 449
• Main Authors: Amin, Firman Zulkifli, Yamashita, Toshiharu, Ohneda, Osamu
• Format: Article
• Language: English
• Subjects: Alveolar; Alveoli; Angiopoietin; Animal models; Animals; Apoptosis; Basic Helix-Loop-Helix Transcription Factors; Cadherins; Cell adhesion & migration; Cell adhesion molecules; Double-mutant mice; Endothelial Cells; Endothelium; Gene expression; HIF-2α; HIF-3α; Homeostasis; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-inducible factors; Laboratories; Lung; Lungs; Mice; Mice, Inbred C57BL; Mice, Knockout; Morphogenesis; Polymerase chain reaction; Pulmonary Alveoli - growth & development; Research Note; Rodents; Transcription Factors - genetics; Vascular cell adhesion molecule 1; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A
• ISSN: 1756-0500; 1756-0500
• DOI: 10.1186/s13104-018-3563-7

Earlier studies from our group using hypoxia-inducible factor 3α knockout mice showed impairments in lung remodeling and lung endothelial cells. Another research from our group demonstrated that impaired expression of hypoxia-inducible factor 2α induced compensatory expression of hypoxia-inducible factor 1α in hypoxia-inducible factor 2α knockdown mice. The present study uncovers more insights by extending the investigation, utilizing mice with both hypoxia-inducible factor 3α knockout and hypoxia-inducible factor 2α knockdown. No mice with both hypoxia-inducible factor 3α knockout and hypoxia-inducible factor 2α knockdown died immediately after birth. The mice with both hypoxia-inducible factor 3α knockout and hypoxia-inducible factor 2α knockdown exhibited impaired alveolar sacs and lung alveolar structure and decreased endothelial cell numbers. Analysis of relative mRNA expression revealed depressed expressions of hypoxia-inducible factor 1α, vascular cell adhesion molecule 1, vascular endothelial cadherin, angiopoietin 2, Tie-2, and vascular endothelial growth factor in the lungs of mice with both hypoxia-inducible factor 3α knockout and hypoxia-inducible factor 2α knockdown compared to that in wild-type mice. Further analysis is needed to elucidate the impaired development occurred in the lung endothelial cells.