DJ ‐1 regulates astrocyte activation through miR ‐155/ SHP ‐1 signaling in cerebral ischemia/reperfusion injury

作者：Ying Xue, Yuan Wang, Tianyi Chen, Li Peng, Chenglong Wang, Gui-Jun Xue, Shanshan Yu · 发表于：Journal of Neurochemistry · 年份：2024 · DOI：10.1111/jnc.16230 · 被引用次数：8 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、MicroRNA in disease regulation

Reactive astrocyte activation in the context of cerebral ischemia/reperfusion (I/R) injury gives rise to two distinct subtypes: the neurotoxic A1 type and the neuroprotective A2 type. DJ-1 (Parkinson disease protein 7, PARK7), originally identified as a Parkinson's disease-associated protein, is a multifunctional anti-oxidative stress protein with molecular chaperone and signaling functions. SHP-1 (Src homology 2 domain-containing phosphatase-1) is a protein tyrosine phosphatase closely associated with cellular signal transduction. miR-155 is a microRNA that participates in cellular functions by regulating gene expression. Recent studies have uncovered the relationship between DJ-1 and astrocyte-mediated neuroprotection, which may be related to its antioxidant properties and regulation of signaling molecules such as SHP-1. Furthermore, miR-155 may exert its effects by influencing SHP-1, providing a potential perspective for understanding the molecular mechanisms of stroke. A middle cerebral artery occlusion/reperfusion (MCAO/R) model and an oxygen-glucose deprivation/reperfusion (OGD/R) model were established to simulate focal cerebral I/R injury in vivo and in vitro, respectively. The in vivo interaction between DJ-1 and SHP-1 has been experimentally validated through immunoprecipitation. Overexpression of DJ-1 attenuates I/R injury and suppresses miR-155 expression. In addition, inhibition of miR-155 upregulates SHP-1 expression and modulates astrocyte activation phenotype....