RT Journal Article
SR Electronic
T1 Loss of Wip1 aggravates brain injury after ischaemia/reperfusion by overactivating microglia
JF Stroke and Vascular Neurology
JO Stroke Vasc Neurol
FD BMJ Publishing Group Ltd
SP 344
OP 351
DO 10.1136/svn-2020-000490
VO 6
IS 3
A1 Feng Yan
A1 Xiang Cheng
A1 Ming Zhao
A1 Shenghui Gong
A1 Ying Han
A1 Liping Ding
A1 Di Wu
A1 Yumin Luo
A1 Wei Zuo
A1 Lingling Zhu
A1 Ming Fan
A1 Xunming Ji
YR 2021
UL http://svn.bmj.com/content/6/3/344.abstract
AB Background and purpose The inflammatory response mediated by microglia/macrophages is closely related to cerebral ischaemia/reperfusion injury. Wild-type p53-induced protein phosphatase 1 (Wip1), a serine/threonine phosphatase, is expressed in various tissues. A growing number of reports have suggested that Wip1 is a negative regulator of inflammation in peripheral tissue; however, its role in the central nervous system (CNS) remains unclear. This study aimed to clarify whether Wip1 can inhibit CNS inflammation by regulating microglia/macrophage functions after ischaemic injury.Methods A model of middle cerebral artery occlusion and reperfusion was established in mice. CNS inflammation was simulated by lipopolysaccharide treatment of primary microglia. Laser speckle imaging was used to monitor regional cerebral blood flow. Behavioural outcomes were assessed with a TreadScan gait analysis system. TTC staining was used to evaluate the infarct volume, and western blotting and immunofluorescence staining were applied to detect the phenotypical transformation of microglia. ELISA was performed to detect the levels of inflammatory factors.Results Wip1 expression was increased after ischaemia/reperfusion. Wip1-knockout (KO) mice displayed more severe brain injury than wild-type mice, as indicated by aggravated motor dysfunction, greater brain infarct volumes and higher expression of inflammatory cytokines (interleukin-6 and tumour necrosis factor alpha) in the brain. We also found that Wip1 depletion increased microglial/macrophage activation in both in vitro and in vivo models, which all showed activation of microglia/macrophages. Lentivirus-Ppm1d reversed the injury induced by Wip1-KO.Conclusions Our results suggest that Wip1 may inhibit neuroinflammation by inhibiting microglial/macrophage activation after brain ischaemia/reperfusion injury.Data are available upon reasonable request. Data are available upon reasonable request.