title: WIP1 Phosphatase Plays a Critical Neuroprotective Role in Brain Injury Induced by High-Altitude Hypoxic Inflammation.
abstract: The hypobaric hypoxic environment in high-altitude areas often aggravates the severity of inflammation and induces brain injury as a consequence. However, the critical genes regulating this process remain largely unknown. The phosphatase wild-type p53-induced phosphatase 1 (WIP1) plays important roles in various physiological and pathological processes, including the regulation of inflammation in normoxia, but its functions in hypoxic inflammation-induced brain injury remain unclear. Here, we established a mouse model of this type of injury and found that WIP1 deficiency augmented the release of inflammatory cytokines in the peripheral circulation and brain tissue, increased the numbers of activated microglia/macrophages in the brain, aggravated cerebral histological lesions, and exacerbated the impairment of motor and cognitive abilities. Collectively, these results provide the first in vivo evidence that WIP1 is a critical neuroprotector against hypoxic inflammation-induced brain injury.
authors.affiliation: Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
authors.forename: Dahu
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.|Navy General Hospital of the PLA, Beijing, 100048, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
authors.forename: Yunling
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
authors.forename: Lun
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.|Air Force General Hospital of the PLA, Beijing, 100142, China.
authors.forename: Yiyao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
authors.forename: Kuiwu
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China. fanmingchina@126.com.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China. fanmingchina@126.com.|Beijing Institute for Brain Disorders, Beijing, 100069, China. fanmingchina@126.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing, 100850, China. linglingzhu@hotmail.com.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China. linglingzhu@hotmail.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000532:Altitude Sickness / Q000150:complications / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001930:Brain Injuries / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D000860:Hypoxia / Q000150:complications / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000066829:Neuroprotection / Q000502:physiology*; D000071636:Protein Phosphatase 2C / Q000172:deficiency / Q000502:physiology*
chemical_list: C000607468:Ppm1d protein, mouse; D000071636:Protein Phosphatase 2C
keywords: Brain injury; Hypobaric hypoxia; Inflammation; Lipopolysaccharide; WIP1 phosphatase