ER Stress is Involved in Mast Cells Degranulation via IRE1 alpha/miR-125/ Lyn Pathway in an Experimental Intracerebral Hemorrhage Mouse Model

作者全名："Yang, Zhengyu; Huang, Juan; Liao, Yuhui; Gan, Shengwei; Zhu, Shujuan; Xu, Shiye; Shu, Yue; Lu, Weitian"

作者地址："[Yang, Zhengyu; Huang, Juan; Liao, Yuhui; Gan, Shengwei; Zhu, Shujuan; Xu, Shiye; Shu, Yue; Lu, Weitian] Chongqing Med Univ, Basic Med Coll, Dept Anat, Chongqing 400016, Peoples R China; [Yang, Zhengyu; Huang, Juan; Liao, Yuhui; Gan, Shengwei; Zhu, Shujuan; Xu, Shiye; Shu, Yue; Lu, Weitian] Chongqing Med Univ, Basic Med Coll, Inst Neurosci, Chongqing, Peoples R China"

通信作者："Lu, WT (通讯作者)，Chongqing Med Univ, Basic Med Coll, Dept Anat, Chongqing 400016, Peoples R China.; Lu, WT (通讯作者)，Chongqing Med Univ, Basic Med Coll, Inst Neurosci, Chongqing, Peoples R China."

来源：NEUROCHEMICAL RESEARCH

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000756499600001

JCR分区：Q2

影响因子：4.4

年份：2022

卷号：47

期号：6

开始页：1598

结束页：1609

文献类型：Article

关键词：Intracerebral hemorrhage; Neuroinflammation; Mast cell; IRE1 alpha; miR-125; Lyn

摘要："The degranulation of mast cells accounts for the development of neuroinflammation following intracerebral hemorrhage (ICH). Inhibition of IRE1 alpha, a sensor signaling protein related to endoplasmic reticulum stress, has been shown to exert anti-inflammatory effects in several neurological diseases. The objective of this study was to investigate the effects of IRE1 alpha inhibition on mast cells degranulation in an ICH mouse model and to explore the contribution of miR-125/Lyn pathway in IRE1 alpha-mediated mast cells degranulation. Male mice were subjected to ICH by intraparenchymal injection of autologous blood. STF083010, an inhibitor of IRE1 alpha, was administered intranasally at 1 h after ICH induction. AntimiR-125 was delivered by intracerebroventricular (i.c.v.) injection prior to ICH induction to elucidate the possible mechanisms. Western blot analysis, immunofluorescence staining, neurological test, hematoma volume, brain water content, toluidine blue staining and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) were performed. Endogenous phosphorylated IRE1 alpha (p-IRE1 alpha), tryptase, interleukin-17A (IL-17A), tumor necrosis factor alpha (TNF-alpha) and tryptase mRNA were increased in time dependent manner while miR-125b-2-3p was decreased after ICH. Inhibition of IRE1 alpha, with STF083010, remarkably reduced brain water content, improved neurological function, decreased hematoma volume, upregulated the expression of miR-125b-2-3p, decreased the number of mast cells, and downregulated the protein expression of Lyn kinase, XBP1s (spliced X-box binding protein-1), tryptase, IL-17A and TNF-alpha. The downregulation of Lyn kinase, tryptase, IL17A, TNF-alpha, and decreased mast cells number were reversed by antimiR-125. The present findings demonstrate that IRE1a inhibition attenuates mast cells degranulation and neuroinflammation, at least partially, through IRE1 alpha/miR-125/Lyn signaling pathway after ICH."

基金机构："National Natural Science Foundation of China [NSFC 81601051, NSFC 82171457]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (NSFC 81601051, NSFC 82171457)."