WIP1 Phosphatase Plays a Critical Neuroprotective Role in Brain Injury Induced by High-Altitude Hypoxic Inflammation
WIP1 Phosphatase Plays a Critical Neuroprotective Role in Brain Injury Induced by High-Altitude Hypoxic Inflammation
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WIP1 磷酸酶在高原缺氧炎症引起的脑损伤中发挥关键的神经保护作用
DOI：
10.1007/s12264-016-0095-9
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发表时间：
2017-06-01
影响因子：
5.6
通讯作者：
Zhu, Lingling
中科院分区：
文献类型：
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作者：
Li, Dahu;Zhang, Lijun;Zhu, Lingling
高海拔地区的低压缺氧环境常常会加重炎症的严重程度，并进而导致脑损伤。然而，调节这一过程的关键基因在很大程度上仍然未知。野生型p53诱导的磷酸酶1（WIP1）在各种生理和病理过程中发挥着重要作用，包括在常氧状态下对炎症的调节，但其在缺氧炎症诱导的脑损伤中的功能仍不清楚。在此，我们建立了这种损伤的小鼠模型，发现WIP1缺失会增加外周循环和脑组织中炎性细胞因子的释放，增加脑中活化的小胶质细胞/巨噬细胞的数量，加重脑组织学损伤，并加剧运动和认知能力的损害。总之，这些结果首次在体内提供了证据，表明WIP1是对抗缺氧炎症诱导的脑损伤的关键神经保护因子。
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 firstin vivoevidence that WIP1 is a critical neuroprotector against hypoxic inflammation-induced brain injury.