摘要
目的探讨卵巢肿瘤结构域蛋白3敲除(OTUD3^(-/-))小鼠黑质核因子κB(NF-κB)相关炎症因子表达的变化及其机制。方法分别选取3只24月龄OTUD3^(-/-)雄性小鼠(OTUD3^(-/-)组)及其同窝野生型(WT)雄性小鼠(WT组)的双侧黑质组织,采用转录组学测序(RNA-seq)技术筛选差异表达基因(DEGs),应用KEGG通路富集分析先天免疫应答中NF-κB相关炎症因子表达变化,并采用实时荧光定量PCR(RT-qPCR)技术对筛选出的DEGs进行验证。结果KEGG通路富集分析显示,与WT组小鼠相比,OTUD3^(-/-)组小鼠黑质NF-κB经典通路上的脂多糖结合蛋白(LBP)和环氧合酶2(COX2)表达上调,非经典通路上的C-C基序趋化因子19(CCL19)和细胞黏附因子1(ICAM1)表达也均上调。RT-qPCR验证结果显示,与WT组相比,OTUD3^(-/-)组小鼠黑质LBP和COX2 mRNA水平明显上调(t=7.81、3.11,P<0.05)。结论OTUD3^(-/-)小鼠黑质区可能通过上调NF-κB相关炎症因子LBP、COX2、CCL19和ICAM1基因的表达水平,参与神经炎症反应的调控。
Objective To investigate the changes in the expression of nuclear factor-kappa B(NF-κB)-related inflammatory factors in the substantia nigra of mice with ovarian tumor domain-containing protein 3 knockout(OTUD3^(-/-))and related mechanisms.Methods Three male OTUD3^(-/-)mice,aged 24 months,were selected as OTUD3^(-/-)group,and their wild-type(WT)male littermates were selected as WT group.The substantia nigra tissue at both sides was collected,and the RNA-seq technique was used to screen out differently expressed genes(DEGs).The KEGG pathway enrichment analysis was used to analyze the changes in the expression of NF-κB-related inflammatory factors in innate immune response,and quantitative real-time PCR(RT-qPCR)was used for validation of the DEGs screened out.Results The KEGG pathway enrichment analysis showed that compared with the WT group,the OTUD3^(-/-)group had significant upregulation of lipopolysaccharide-binding protein(LBP)and cyclooxygenase 2(COX2)in the NF-κB canonical pathway,as well as significant upregulation of C-C motif chemokine 19(CCL19)and intercellular adhesion molecule-1(ICAM1)in the NF-κB noncanonical pathway.The results of RT-qPCR also showed that compared with the WT group,the OTUD3^(-/-)group had significant upregulation of the mRNA expression levels of LBP and COX2(t=7.81,3.11,P<0.05).Conclusion In OTUD3^(-/-)mice,the substantia nigra participates in the regulation of neuroinflammatory response possibly by upregulating the gene expression levels of the NF-κB-related inflammatory factors LBP,COX2,CCL19,and ICAM1.
作者
高艺峻
贾凤菊
焦倩
陈曦
杜希恂
姜宏
GAO Yijun;JIA Fengju;JIAO Qian;CHEN Xi;DU Xixun;JIANG Hong(State Key(Cultivation)Disciplines of Physiology,Qingdao University,Qingdao 2666071,China)
出处
《精准医学杂志》
2021年第2期95-98,共4页
Journal of Precision Medicine
基金
国家自然科学基金面上项目(31771110)
山东省自然科学基金重大基础研究项目(ZR2019ZD31)
山东省自然科学基金青年基金(ZR202-0QH125)。
