title: Hypertonicity contributes to seawater aspiration-induced lung injury: Role of hypoxia-inducible factor 1α.
abstract: Drowning is an important public health problem, but the mechanism of acute lung injury induced by near-drowning is rarely reported. The aim of this study is to investigate the role of hypertonicity and HIF-1α in seawater aspiration-induced lung injury. Diverse solutions were used to study the effect of hypertonicity on hypoxia, inflammation, vascular leakage, edema, and HIF-1α expression in lungs of rats. The relationship between hypertonicity and hypoxia, when they induced HIF-1α, was studied and the roles of ATM, PI3K, and p38 in the course of hypertonicity inducing HIF-1α were investigated. At last, our conclusion was verified with HIF-1α inhibitor and inducer in seawater aspiration rats. The results showed that hypertonicity, but not isotonicity and hypotonicity, promoted hypoxia, inflammation, vascular leakage, edema, and HIF-1α expression in lungs. Hypertonicity not only induced HIF-1α in a time- and dose-dependent manner but also could increase HIF-1α synergistically with hypoxia in AEC. Furthermore, hypertonicity increased HIF-1α by promoting its mRNA expression through both ATM and PI3K activation and by suppressing its protein degradation through p38 activation. During hyperosmotic stress, the increased HIF-1α promoted the production of the inflammatory cytokines in NR8383 and elevated monolayer permeability through increasing VEGF in RLMVEC. In conclusion, hypertonicity induced by aspirated seawater aggravated lung injury through increasing HIF-1α which promoted inflammation and edema in lung tissues in rats.
authors.affiliation: 1Department of Respiration, Tangdu Hospital, Fourth Military Medical University , Xi'an , PR China.
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Wang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.forename: Rong-Gang
authors.initials: RG
authors.lastname: Xi
authors.forename: Feng
authors.initials: F
authors.lastname: Han
authors.forename: Wang-Ping
authors.initials: WP
authors.lastname: Li
authors.forename: Lijing
authors.initials: L
authors.lastname: Fu
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Li
authors.forename: Faguang
authors.initials: F
authors.lastname: Jin
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism* / Q000503:physiopathology*; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D004332:Drowning / Q000378:metabolism / Q000503:physiopathology; D004487:Edema / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D015701:Near Drowning / Q000378:metabolism / Q000503:physiopathology; D009997:Osmotic Pressure / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012623:Seawater; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D064007:Ataxia Telangiectasia Mutated Proteins; D048051:p38 Mitogen-Activated Protein Kinases
keywords: acute lung injury; hypoxia-inducible factor 1α; osmotic pressure; seawater drowning