Myricitrin inhibits fibroblast-like synoviocyte-mediated rheumatoid synovial inflammation and joint destruction by targeting AIM2.
Myricitrin inhibits fibroblast-like synoviocyte-mediated rheumatoid synovial inflammation and joint destruction by targeting AIM2.
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杨梅苷通过靶向 AIM2 抑制成纤维细胞样滑膜细胞介导的类风湿滑膜炎症和关节破坏
DOI：
10.3389/fphar.2022.905376
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发表时间：
2022
影响因子：
5.6
通讯作者：
Xu, Hanshi
中科院分区：
文献类型：
--
作者：
Shen, Chuyu;Xu, Meilin;Xu, Siqi;Zhang, Shuoyang;Lin, Wei;Li, Hao;Zeng, Shan;Qiu, Qian;Liang, Liuqin;Xiao, Youjun;Xu, Hanshi
目的：探讨杨梅素(MyR)对类风湿关节炎(RA)成纤维细胞样滑膜细胞(FLS)介导的滑膜炎症和关节破坏的调节作用及其机制。方法：从类风湿关节炎患者的滑膜组织中分离出FLSS。用定量RT-qPCR法检测基因表达。免疫组织化学法或Western印迹法检测蛋白表达。Annexin-PI染色检测细胞凋亡。用EDU掺入法检测RA FLS的增殖情况。用Transwell法检测RA FLS细胞的迁移和侵袭能力。通过RNA测序分析确定了MyR的潜在靶点。在胶原性关节炎(CIA)模型中评估了MyR的体内效应。结果：MYR治疗可抑制RA FLSS片状脂体的形成、迁移和侵袭，但不能抑制细胞的凋亡和增殖。降低肿瘤坏死因子-α诱导的CCL2、IL-6、IL-8、MMP1、MMP3、MMP13的表达。RNA-seq分析结果表明，AIM2基因可能是类风湿关节炎FLSS中MyR的靶基因。此外，与健康对照组相比，AIM2在RA患者的滑膜组织和Fls中的表达水平更高。AIM2基因敲除也可抑制RA FLS的迁移、侵袭、细胞因子和基质金属蛋白酶的表达。此外，MyR处理或AIM2基因敲除均可降低肿瘤坏死因子-α刺激诱导的AKT的磷酸化。重要的是，MyR给药缓解了关节炎症状，并抑制了CIA小鼠滑膜中AIM2的表达。结论：MYR具有抗炎、抗侵袭作用，为MYR治疗RA提供了依据。
Objective: To explore the effect and underlying mechanism of Myricitrin (Myr) in regulating fibroblast-like synoviocyte (FLS)-mediated synovitis and joint destruction in RA. Methods: FLSs were isolated from synovial tissues from patients with RA. Gene expression was measured using quantitative RT-qPCR. Protein expression was detected by immunohistochemistry or Western blot. Cell apoptosis was performed by an Annexin-PI staining assay. EdU incorporation was used to assess the proliferation of RA FLS. Transwell assay was used to characterize the cell migration and invasion ability of RA FLS. The potential target of Myr was identified by RNA sequencing analysis. The in vivo effect of Myr was assessed in a collagen-induced arthritis (CIA) model. Results: Myr treatment inhibited the lamellipodia formation, migration, and invasion, but not the apoptosis and proliferation, of RA FLSs. Myr also reduced the expression of CCL2, IL-6, IL-8, MMP-1, MMP-3, and MMP-13 induced by TNF-α. The RNA-seq results indicated that AIM2 may be a target gene of Myr in RA FLSs. Furthermore, compared to healthy controls, AIM2 expression showed higher levels in synovial tissues and FLSs from RA patients. AIM2 knockdown also inhibited RA FLS migration, invasion, cytokine, and MMP expression. In addition, either Myr treatment or AIM2 knockdown reduced the phosphorylation of AKT induced by TNF-α stimulation. Importantly, Myr administration relieved arthritis symptoms and inhibited AIM2 expression in the synovium of CIA mice. Conclusion: Our results indicate that Myr exerts an anti-inflammatory and anti-invasion effect in RA FLSs and provide evidence of the therapeutic potential of Myr for RA.
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影响因子：
3.7
作者：
Gao, Jing;Liu, Cuicui;Wang, Rongmei
通讯作者：
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DOI：
10.1080/14756366.2020.1754813
发表时间：
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影响因子：
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影响因子：
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作者：
Wang B;Hao D;Zhang Z;Gao W;Pan H;Xiao Y;He B;Kong L
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影响因子：
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DOI：
10.22037/ghfbb.v13i3.1782
发表时间：
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影响因子：
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作者：
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