Ski Regulates the Inflammatory Response of Reactive Astrocytes Induced by Oxygen Glucose Deprivation/Reoxygenation (OGD/R) Through the NF-?B Pathway
Ski Regulates the Inflammatory Response of Reactive Astrocytes Induced by Oxygen Glucose Deprivation/Reoxygenation (OGD/R) Through the NF-?B Pathway
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DOI：
10.1016/j.neuroscience.2022.02.015
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发表时间：
2022-04-01
期刊：
影响因子：
3.3
通讯作者：
Zhang, Hai-hong
中科院分区：
文献类型：
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作者：
Liao, Hai-Yang;Ran, Rui;Zhang, Hai-hong
脊髓损伤（Spinal cord injury，SCI）是一种常见的神经系统疾病，包括原发性和继发性损伤。脊髓损伤后神经元炎症是脊髓损伤最重要的病理过程，是损伤后神经功能恢复的化学屏障。Ski是一种进化上保守的功能性转录调节蛋白，在SCI后反应性星形胶质细胞中上调，并调节星形胶质细胞的生物学特征。然而，其在脊髓缺血后由反应性星形胶质细胞引发的胶质炎症反应中的作用及其确切机制尚不清楚。本研究旨在探讨Ski在缺氧缺糖/复氧（OGD/R）诱导的反应性星形胶质细胞炎症反应中的作用及其机制。在ODG/R模型中，Ski表达上调。相反，Ski上调伴随着iNOS、IL-1 β、IL-6、TNF-α和其他炎症相关因子水平的增加。这些结果表明，星形胶质细胞引发的炎症反应在OGD/R刺激的星形胶质细胞中显著增强。用Ski特异性siRNA转染星形胶质细胞以敲除Ski，随后减弱OGD诱导的星形胶质细胞触发的炎症。我们的研究结果还表明，Ski下调通过抑制NF-κ B信号通路的活性下调iNOS，IL-113，IL-6和TNF-α在OGD/R诱导的反应性星形胶质细胞中的表达。总之，下调Ski可以通过抑制NF-κ B通路的活性来有效地抑制SCI中的胶质炎症。这些发现表明，Ski是SCI后炎症反应的一个有前途的治疗靶点。总之，Ski下调可通过抑制NF-κ B B通路的活性有效抑制SCI中的胶质炎症。这些发现表明，Ski可能作为一个有前途的目标，为SCI后的炎症反应的治疗。(C)2022 IBRO。由爱思唯尔有限公司出版。保留所有权利。
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-1 beta, IL-6, TNF-alpha, and other inflammation-related factors. These results indicated that the inflammatory response triggered by astrocytes was significantly enhanced in OGD/Rstimulated 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-113, IL-6, and TNF-alpha in OGD/R-induced reactive astrocytes by inhibiting the activity of the NF-kappa B signaling pathway. In conclusion, downregulation of Ski can effectively inhibit glial inflammation in SCI by inhibiting the activity of the NF-kappa B 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-kappa B pathway. These findings suggest that Ski might serve as a promising target for the treatment of inflammatory responses after SCI. (C) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.