Sirt1 regulates microglial activation and inflammation following oxygen-glucose deprivation/reoxygenation injury by targeting the Shh/Gli-1 signaling pathway

作者全名："Liao, Hongyan; Huang, Jiagui; Liu, Jie; Zhu, Huimin; Chen, Yue; Li, Xuemei; Wen, Jun; Yang, Qin"

作者地址："[Liao, Hongyan; Huang, Jiagui; Liu, Jie; Zhu, Huimin; Chen, Yue; Li, Xuemei; Wen, Jun; Yang, Qin] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, 1 Youyi Rd, Chongqing 400016, Peoples R China"

通信作者："Yang, Q (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：MOLECULAR BIOLOGY REPORTS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000926052900003

JCR分区：Q4

影响因子：2.8

年份：2023

卷号：50

期号：4

开始页：3317

结束页：3327

文献类型：Article

关键词：Microglial activation; Neuroinflammation; Oxygen-glucose deprivation/reoxygenation; Sirtuin 1; Sonic hedgehog signaling pathway

摘要："Background Cerebral ischemic injury leads to over-activation of microglia, which release pro-inflammatory factors that deteriorate neurological function during the acute phase of stroke. Thus, inhibiting microglial over-activation is crucial for reducing ischemic injury. Sirtuin 1 (Sirt1) has been shown to play a critical role in stroke, neurodegenerative diseases and aging. However, the effect of Sirt1 on the regulation of microglial activation following cerebral ischemic injury, as well as the underlying mechanism, remain unknown. Therefore, the purpose of the present study is to mainly investigate the effect of Sirt1 on oxygen-glucose deprivation/reoxygenation (OGD/R)-treated N9 microglia following treatment with the Sirt1 agonists resveratrol and SRT1720 and the Sirt1 antagonist sirtinol. Methods Cell viability, Apoptosis, activation and inflammatory responses of microglia, expressions and activity of Shh signaling pathway proteins were detected by Cell Counting Kit 8, Flow Cytometry, immunocytochemistry, ELISA, and Western blotting, respectively. Results The results demonstrated that treatment with resveratrol or SRT1720 could inhibit the activation of microglia and inflammation during OGD/R. Moreover, these treatments also led to the translocation of the GLI family zinc finger-1 (Gli-1) protein from the cytoplasm to the nucleus and upregulated the expression of Sonic hedgehog (Shh), Patched homolog-1 (Ptc-1), smoothened frizzled class receptor and Gli-1. By contrast, the inhibition of Sirt1 using sirtinol had the opposite effect. Conclusion These findings suggested that Sirt1 may regulate microglial activation and inflammation by targeting the Shh/Gli-1 signaling pathway following OGD/R injury."

基金机构："National Nature Science Foundation of China [81671309, 81971229]; Tibet Nature Science Foundation of Tibet [XZ2017ZR-ZY026]; Postgraduate Research and Innovation Project of Chongqing [CYS17148]"

基金资助正文："The present study was supported by several grants named the National Nature Science Foundation of China (Grant No. 81671309 and 81971229), the Tibet Nature Science Foundation of Tibet (grant no. XZ2017ZR-ZY026) and the Postgraduate Research and Innovation Project of Chongqing (Grant No. CYS17148) respectively."