雷公藤内酯通过 Hippo 信号通路调节中性粒细胞功能,从而缓解类风湿性关节炎的病情进展

IF 4.7 Q2 IMMUNOLOGY Journal of Translational Autoimmunity Pub Date : 2024-05-03 DOI:10.1016/j.jtauto.2024.100242
Pengyuan Liu , Huiyang Liu , Yali Sang , Lingyan Zhu , Peiyao Zhang , Chunyan Pang , Yongfu Wang , Li Bai
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引用次数: 0

摘要

类风湿性关节炎(RA)是一种慢性自身免疫性疾病,以关节炎症性改变为特征,其病因尚不清楚。目前已经确定,调节性细胞死亡(RCD)和中性粒细胞迁移在类风湿性关节炎的发病机制中发挥着重要作用。威斯康辛科植物三尖杉(Tripterygium wilfordii Hook.f)(TwHF)是从其根部提取的一种总皂苷,具有很强的抗炎和免疫调节作用,已被用作临床治疗 RA 的基础药物。尽管TwHF治疗效果良好,但其作用机制仍不清楚。多项研究表明,以TwHF为主要成分的三叶皂苷类药物在临床治疗RA方面取得了很好的疗效。研究还发现,TwHF可影响细胞RCD、细胞迁移、细胞增殖以及与细胞凋亡相关的Hippo信号通路。在本研究中,我们首先通过网络药理学和转录组分析,分析了RA患者中性粒细胞的RCD和迁移差异。随后,我们利用电子显微镜、免疫荧光等方法确定了中性粒细胞的RCD表型。在胶原诱导的关节炎(CIA)模型中,我们证明了特利托利(Triptolide,TwHF 的主要活性成分)可以通过减少骨破坏和中性粒细胞的浸润来缓解关节炎的进展。此外,体外实验表明,曲托列特能诱导中性粒细胞凋亡,抑制中性粒细胞胞外捕获物(NET)的形成,并以依赖 Hippo 通路的方式阻碍中性粒细胞的迁移过程。综上所述,这些研究结果表明,雷公藤内酯具有治疗风湿性关节炎的潜力,并为风湿性关节炎的中药临床应用提供了理论支持。
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Triptolide regulates neutrophil function through the Hippo signaling pathway to alleviate rheumatoid arthritis disease progression

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammatory changes in the joints, the etiology of which is unclear. It is now well established that regulated cell death (RCD) and migration of neutrophils play an important role in the pathogenesis of RA. Tripterygium wilfordii Hook.f (TwHF) is a total saponin extracted from the root of Tripterygium wilfordii Hook.f, a plant of the family Wesleyanaceae, which has strong anti-inflammatory and immunomodulatory effects and has been used as a basic drug in the clinical treatment of RA. Despite the good efficacy of TwHF treatment, the mechanism of action of TwHF remains unclear. Several studies have demonstrated that the drug tripterygium glycosides, in which TwHF is the main ingredient, has achieved excellent efficacy in the clinical treatment of RA. Investigations have also found that TwHF can affect cellular RCD, cell migration, cell proliferation, and the apoptosis-related Hippo signaling pathway. In this study, we first analyzed the RCD and migration differences of neutrophils in patients with RA through network pharmacology and transcriptome analysis. Subsequently, we used electron microscopy, immunofluorescence, and other methods to identify the RCD phenotype of neutrophils. In collagen-induced arthritis (CIA) model, we demonstrated that Triptolide (the main active ingredient in TwHF) could alleviate the progression of arthritis by reducing the bone destruction and the infiltration of neutrophils. Furthermore, in vitro experiments showed that Triptolide induced neutrophil apoptosis, inhibited the formation of neutrophil extracellular traps (NETs), and impeded the neutrophil migration process in a Hippo pathway-dependent manner. Taken together, these findings indicate that Triptolide has potential for treating RA and provide theoretical support for the clinical application of TwHF, as a traditional Chinese medicine, in RA.

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来源期刊
Journal of Translational Autoimmunity
Journal of Translational Autoimmunity Medicine-Immunology and Allergy
CiteScore
7.80
自引率
2.60%
发文量
33
审稿时长
55 days
期刊最新文献
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