ZNRF3 Regulates Collagen-Induced Arthritis Through NF-kB and Wnt Pathways
ZNRF3 Regulates Collagen-Induced Arthritis Through NF-kB and Wnt Pathways
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ZNRF3 通过 NF-kB 和 Wnt 通路调节胶原诱导的关节炎
DOI：
10.1007/s10753-020-01193-1
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发表时间：
2020-03-03
期刊：
影响因子：
5.1
通讯作者：
Zhao, Dong Bao
中科院分区：
文献类型：
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作者：
Liang, Jing Jing;Li, Hao Ran;Zhao, Dong Bao
虽然E3泛素连接酶锌和环指3（ZNRF 3）负调控Wnt信号通路，但其在类风湿性关节炎（RA）中的功能尚不清楚。在这里，ZNRF 3对胶原诱导的关节炎（CIA）的小鼠模型和从RA患者获得的人成纤维细胞样滑膜细胞（FLS）的作用和机制进行了确定。我们的研究结果表明，ZNRF 3在组织和FLS中的高表达相比，创伤患者。慢病毒介导的ZNRF 3沉默诱导的细胞凋亡降低了细胞活力，并显著减轻了RA-FLSsviatumor necrosis-α（TNF-α）的炎症反应。此外，ZNRF 3的沉默减少了CIA小鼠模型中的膝关节损伤，也降低了TNF-α、IL-1β和IL-6的水平。RA-FLS中Wnt和NF-κB通路之间的相互作用介导了这些作用。
Although the E3 ubiquitin ligase Zinc and ring finger 3 (ZNRF3) negatively regulates the Wnt signaling pathway, its function in rheumatoid arthritis (RA) is elusive. Here, the effects and the mechanism of ZNRF3 on a mouse model of collagen-induced arthritis (CIA) and human fibroblast-like synoviocytes (FLS) obtained from RA patients were determined. Our results showed that ZNRF3 was highly expressed in tissues and FLSs compared to trauma patients. Lentivirus-mediated silencing of ZNRF3 induced apoptosis decreased cell viability and significantly attenuated inflammation in RA-FLSsviatumor necrosis-α (TNF-α). Additionally, silencing of ZNRF3 reduced knee joint damage and also decreased the level of TNF-α, IL-1β, and IL-6 in the CIA mouse model. These effects were mediated by the crosstalk between Wnt and NF-κB pathways in RA-FLS.