Dishevelled2 promotes apoptosis and inhibits inflammatory cytokine secretion in rheumatoid arthritis fibroblast-like synoviocytes through crosstalk with the NF-κB pathway.
Dishevelled2 promotes apoptosis and inhibits inflammatory cytokine secretion in rheumatoid arthritis fibroblast-like synoviocytes through crosstalk with the NF-κB pathway.
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Dishevelled2 通过与 NF-kappa B 通路串扰促进类风湿性关节炎成纤维细胞样滑膜细胞凋亡并抑制炎症细胞因子分泌
DOI：
10.18632/oncotarget.15172
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发表时间：
2017-02-21
期刊：
影响因子：
--
通讯作者：
Zhao DB
中科院分区：
文献类型：
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作者：
Liu XZ;Fan J;Qi K;Liu SP;Xu WD;Gao Y;Gu XD;Li J;Bai CG;Shi YQ;Zhang LL;Zhao DB
Dishevelled（Dvl）不仅连接经典Wnt和非经典Wnt通路，而且还可以与其他通路串扰。由于迄今为止在类风湿性关节炎（RA）中没有关于Dvl的系统研究，我们探索了Dvl 2对RA成纤维细胞样滑膜细胞（FLS）中的增殖和炎性细胞因子分泌的影响。检测Dv 12在RA滑膜组织和RA FLS中的表达。Dv 12在胶原诱导的关节炎大鼠和人RA-FLS中过表达。观察细胞凋亡及炎性细胞因子的分泌。评估了RA-FLS中过表达Dvl 2引起的遗传变化和相应的机制。Dvl 2在RA滑膜组织和RA-FLS中过表达。Dvl 2的过表达增加RA-FLS的凋亡并抑制体内和体外的炎性细胞因子分泌，并且Dvl 2抑制抗凋亡基因和炎性基因的表达。Dvl 2可能通过抑制P65的核转位，抑制P65与NF-κB靶基因启动子的结合而发挥作用。我们的研究结果揭示了Dvl 2在调节炎症和RA-FLS细胞凋亡方面的作用未被充分认识，并提供了对Wnt与核因子-κB（NF-κB）途径之间串扰的深入了解。
Dishevelled (Dvl) not only links the canonical Wnt and non-canonical Wnt pathways but can also crosstalk with other pathways. As there is no systematic study to date on Dvl in rheumatoid arthritis (RA), we explored the impact of Dvl2 on proliferation and inflammatory cytokine secretion in RA fibroblast-like synoviocytes (FLSs). Expression of Dvl2 in RA synovial tissue and RA-FLSs was measured. Dvl2 was overexpressed in collagen-induced arthritis rats and human RA-FLSs,. the apoptosis and secretion of inflammatory cytokines were observed. Genetic changes and corresponding mechanisms caused by overexpressing Dvl2 in RA-FLSs were assessed. Dvl2 was found to be overexpressed in RA synovial tissue and RA-FLSs. Overexpression of Dvl2 increased apoptosis and inhibited inflammatory cytokine secretion by RA-FLSs in vivo and in vitro, and Dvl2 inhibited expression of anti-apoptotic and inflammatory genes. One possible mechanism is that Dvl2 decreases the nuclear translocation of P65 and inhibits its ability to bind to the promoters of NF-κB target genes. Our findings reveal an underappreciated role of Dvl2 in regulating inflammation and RA-FLS apoptosis and provide insight into crosstalk between the Wnt and nuclear factor-κB (NF-κB) pathways.