Blockage of the NLRP3 inflammasome by MCC950 inhibits migration and invasion in adenomyosis

IF 3.7 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Reproductive biomedicine online Pub Date : 2024-06-11 DOI:10.1016/j.rbmo.2024.104319

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引用次数: 0

Abstract

Research question

Does the NOD-like receptor protein 3 (NLRP3) inflammasome have an effect in adenomyosis?

Design

Fresh-frozen endometrial tissues and paraffin specimens were obtained from endometrial tissues from patients with adenomyosis and controls. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were applied to assess expression of the NLRP3 inflammasome components. Primary eutopic endometrial stromal cells were isolated from the uteri of patients with adenomyosis. After NLRP3 was knocked down using small interfering RNA, proliferation, invasion and epithelial–mesenchymal transition (EMT) were evaluated using EdU, CCK8, transwell assays and western blot. Importantly, a mouse model of adenomyosis was established to evaluate the effects of the NLRP3 inhibitor MCC950 on the formation of adenomyosis.

Results

Expression of the NLRP3 inflammasome components was elevated in the ectopic or eutopic endometrium of patients with adenomyosis. NLRP3 knockdown inhibited migration, invasion and EMT in endometrial cells and primary endometrial cells (P < 0.0001). MCC950, which blocks the NLRP3 inflammasome, reduced migration and invasion of endometrial cells (P < 0.01) and primary endometrial cells (P < 0.0001) considerably. Importantly, in the mouse model of adenomyosis, MCC950 had a mitigating effect on the severity of adenomyosis (P < 0.01).

Conclusions

NLRP3 was found to enhance migration, invasion and EMT of human endometrial cells in adenomyosis. Notably, the NLRP3 inhibitor MCC950 reduced migration and invasion of endometrial cells effectively. Furthermore, in the mouse model of adenomyosis, MCC950 exhibited a therapeutic effect by alleviating the severity of adenomyosis.

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MCC950 阻断 NLRP3 炎症小体可抑制子宫腺肌病的迁移和侵袭

研究问题NOD样受体蛋白3（NLRP3）炎性体对子宫腺肌症有影响吗？设计从子宫腺肌症患者和对照组患者的子宫内膜组织中获取鲜冻内膜组织和石蜡标本。应用 Western 印迹、实时定量聚合酶链反应（qRT-PCR）和免疫组织化学（IHC）评估 NLRP3 炎性体成分的表达。从子宫腺肌症患者的子宫中分离出原发性异位子宫内膜基质细胞。使用小干扰 RNA 敲除 NLRP3 后，使用 EdU、CCK8、transwell 试验和 Western 印迹法评估了增殖、侵袭和上皮-间质转化（EMT）。重要的是，该研究还建立了子宫腺肌症小鼠模型，以评估 NLRP3 抑制剂 MCC950 对子宫腺肌症形成的影响。敲除 NLRP3 可抑制子宫内膜细胞和原发性子宫内膜细胞的迁移、侵袭和 EMT（P < 0.0001）。阻断 NLRP3 炎性体的 MCC950 能显著减少子宫内膜细胞（P < 0.01）和原代子宫内膜细胞（P < 0.0001）的迁移和侵袭。重要的是，在子宫腺肌病小鼠模型中，MCC950 对子宫腺肌病的严重程度有缓解作用（P < 0.01）。值得注意的是，NLRP3 抑制剂 MCC950 能有效减少子宫内膜细胞的迁移和侵袭。此外，在子宫腺肌病小鼠模型中，MCC950 通过减轻子宫腺肌病的严重程度而显示出治疗效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reproductive biomedicine online 医学-妇产科学

CiteScore

7.20

自引率

7.50%

发文量

391

审稿时长

50 days

期刊介绍： Reproductive BioMedicine Online covers the formation, growth and differentiation of the human embryo. It is intended to bring to public attention new research on biological and clinical research on human reproduction and the human embryo including relevant studies on animals. It is published by a group of scientists and clinicians working in these fields of study. Its audience comprises researchers, clinicians, practitioners, academics and patients. Context: The period of human embryonic growth covered is between the formation of the primordial germ cells in the fetus until mid-pregnancy. High quality research on lower animals is included if it helps to clarify the human situation. Studies progressing to birth and later are published if they have a direct bearing on events in the earlier stages of pregnancy.