Ski Regulates the Inflammatory Response of Reactive Astrocytes Induced by Oxygen Glucose Deprivation/Reoxygenation (OGD/R) Through the NF-κB Pathway

Spinal cord injury (SCI) is a common disease of the nervous system, including primary and secondary injuries. Neuronal inflammation after SCI is the most important pathological process of SCI and a chemical barrier to nerve function recovery after injury. Ski, an evolutionarily conserved functional transcriptional regulator protein, is upregulated in reactive astrocytes after SCI and regulates the biological characteristics of astrocytes. However, its role in the glial inflammatory response triggered by reactive astrocytes after spinal cord ischemia and its exact mechanism remains unclear. This study investigated the role and mechanism of Ski in the inflammatory response triggered by reactive astrocytes induced by oxygen and sugar deprivation/reoxygenation (OGD/R) model in vitro. In the ODG/R model, Ski expression was upregulated. In contrast, Ski upregulation was accompanied by increased levels of iNOS, IL-1β, IL-6, TNF-α, and other inflammation-related factors. These results indicated that the inflammatory response triggered by astrocytes was significantly enhanced in OGD/R-stimulated astrocytes. Astrocytes were transfected with Ski specific siRNA to knock out Ski and subsequently attenuate OGD-induced astrocyte-triggered inflammation. Our results also suggest that Ski downregulation downregulates the expression of iNOS, IL-1β, IL-6, and TNF-α in OGD/R-induced reactive astrocytes by inhibiting the activity of the NF-κB signaling pathway. In conclusion, downregulation of Ski can effectively inhibit glial inflammation in SCI by inhibiting the activity of the NF-κB pathway. These findings suggest that Ski is a promising therapeutic target for inflammatory responses after SCI.In conclusion, Ski downregulation can effectively inhibit glial inflammation in SCI by inhibiting the activity of the NF-κB pathway. These findings suggest that Ski might serve as a promising target for the treatment of inflammatory responses after SCI.