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

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. These findings suggest that DJ‐1 mediates astrocyte activation via the miR‐155/SHP‐1 pathway, playing a pivotal role in the pathogenesis of cerebral ischemia–reperfusion injury. Our results provide a potential way for exploring the pathogenesis of ischemic stroke and present promising targets for pharmacological intervention. [ABSTRACT FROM AUTHOR]