Hypoxia-Inducible Factor (HIF)-1α Promotes Inflammation and Injury Following Aspiration-Induced Lung Injury in Mice.
Journal
Shock (Augusta, Ga.)
ISSN: 1540-0514
Titre abrégé: Shock
Pays: United States
ID NLM: 9421564
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
pubmed:
3
1
2019
medline:
20
8
2020
entrez:
3
1
2019
Statut:
ppublish
Résumé
Acid aspiration-induced lung injury is a common disease in the intensive care unit (ICU) and acute respiratory distress syndrome (ARDS). Hypoxia-inducible factor (HIF)-1α is a major transcription factor responsible for regulating the cellular response to changes in oxygen tension. A clear understanding of the function of HIF-1α in lung inflammatory response is currently lacking. Here, we sought to determine the role of HIF-1α in type 2 alveolar epithelial cells (AEC) in the generation of the acute inflammatory response following gastric aspiration (GA). GA led to profound hypoxia at very early time points following GA. This correlated to a robust increase in HIF-1α, tissue albumin and pro-inflammatory mediators following GA in AECs. The extent of lung injury and the release of pro/anti-inflammatory cytokines were significantly reduced in HIF-1α (-/-) mice. Finally, we report that HIF-1α upregulation of the acute inflammatory response is dependent on NF-κB following GA.
Identifiants
pubmed: 30601332
doi: 10.1097/SHK.0000000000001312
pmc: PMC6591116
mid: NIHMS1517045
doi:
Substances chimiques
Hif1a protein, mouse
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
612-621Subventions
Organisme : NCI NIH HHS
ID : R01 CA148828
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM111305
Pays : United States
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