Circular RNA PTP4A2 regulates microglial polarization through STAT3 to promote neuroinflammation in ischemic stroke

作者：Xingzhi Wang, Shenyang Zhang, Bingchen Lv, Hao Chen, Wei Zhang, Liguo Dong, Lei Bao, Miao Wang, Yan Wang, Wenqi Mao, Likun Cui, Ye Pang, Fei Wang, Fuling Yan, Zuohui Zhang, Guiyun Cui · 发表于：CNS Neuroscience & Therapeutics · 年份：2023 · DOI：10.1111/cns.14512 · 被引用次数：35 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Circular RNAs in diseases、Inflammasome and immune disorders

OBJECTIVE: Microglial polarization plays a critical role in neuroinflammation and may be a potential therapeutic target for ischemic stroke. This study was to explore the role and underlying molecular mechanism of Circular RNA PTP4A2 (circPTP4A2) in microglial polarization after ischemic stroke. METHODS: C57BL/6J mice underwent transient middle cerebral artery occlusion (tMCAO), while primary mouse microglia and BV2 microglial cells experienced oxygen glucose deprivation/reperfusion (OGD/R) to mimic ischemic conditions. CircPTP4A2 shRNA lentivirus and Colivelin were used to knock down circPTP4A2 and upregulate signal transducer and activator of transcription 3 (STAT3) phosphorylation, respectively. Microglial polarization was assessed using immunofluorescence staining and Western blot. RNA pull-down and RNA binding protein immunoprecipitation (RIP) were applied to detect the binding between circPTP4A2 and STAT3. RESULTS: The levels of circPTP4A2 were significantly increased in plasma and peri-infarct cortex in tMCAO mice. CircPTP4A2 knockdown reduced infarct volume, increased cortical cerebral blood flow (CBF), and attenuated neurological deficits. It also decreased pro-inflammatory factors levels in peri-infarct cortex and plasma, and increased anti-inflammatory factors concentrations 24 h post-stroke. In addition, circPTP4A2 knockdown suppressed M1 microglial polarization and promoted M2 microglial polarization in both tMCAO mice and OGD/R-induced BV2 microglial cells. More...