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NLRP3炎症小体激活促进肝星状细胞活化的机制

彭憬 袁维 银思涵 孙克伟

引用本文:
Citation:

NLRP3炎症小体激活促进肝星状细胞活化的机制

DOI: 10.3969/j.issn.1001-5256.2022.11.035
基金项目: 

国家自然科学基金青年基金 81904182;

湖南省自然科学基金 S2020JJ5441

利益冲突声明:所有作者均声明不存在利益冲突。
作者贡献声明:彭憬、孙克伟参与起草和修改文章关键内容;袁维、银思涵对研究的思路有关键贡献。
详细信息
    通信作者:

    孙克伟,Keweisun@aliyun.com

Mechanism of NLRP3 inflammasome promoting hepatic stellate cell activation

Research funding: 

National Science Fund for Distinguished Young Scholar 81904182;

Natural Science Foundation of Hunan Province S2020JJ5441

More Information
  • 摘要: 肝纤维化是慢性肝脏损伤的共同结果,可进展为肝硬化甚至是肝癌,目前尚无有效逆转肝纤维化的手段。在窦周隙中被激活的肝星状细胞转变为肌成纤维细胞并分泌胶原,是肝纤维化进程中的中心事件。NLRP3炎症小体可被各种损伤刺激激活,介导炎症反应和细胞焦亡。近年研究发现NLRP3炎症小体与肝星状细胞活化密切相关。介绍了在各种病理因素刺激下,NLRP3炎症小体在肝星状细胞内不同通路的激活,以及促进胞外炎症微环境的形成,从而介导肝星状细胞活化,在促肝纤维化中发挥重要作用。

     

  • 图  1  NLRP3炎症小体的两步激活模型

    注:微生物组成部分和内源性损伤因子提供启动信号,导致关键转录因子NF-κB激活,随后上调NLRP3和pro-IL-1β表达。细胞外ATP、K+外流、Ca2+内流、ROS的产生、溶酶体损伤、颗粒物质等激活NLRP3炎症小体。dsRNA,双链RNA;TLR4,Toll样受体4;ROS,活性氧;Ox-mtDNA,氧化线粒体DNA;TXNIP,硫氧还蛋白互作蛋白;TWIK2,弱内向整流二孔K+通道2;TRPM2,瞬时受体电位M2通道;P2X7R,嘌呤能离子通道型受体7;MAVS,线粒体抗病毒信号蛋白;CLIC,胞内氯离子通道。

    Figure  1.  Two steps activation model of NLRP3 inflammasome

    图  2  NLRP3炎症小体的激活导致HSC活化

    注:NF-κB,核因子κB;MyD88,髓样分化因子88;MAPK,丝裂原活化蛋白激酶;Dectin-1,树突状细胞相关C型凝集素-1;ERβ,雌激素受体β;ASK1,凋亡信号调节激酶1;Syk脾酪氨酸激酶;SEA,日本血吸虫可溶性虫卵抗原;p66Shc,66 kDa原癌基因Src胶原同源物(Shc)衔接蛋白。

    Figure  2.  Mature NLRP3 inflammasome facilitates the activation of hepatic stellate cell

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  • 收稿日期:  2022-03-29
  • 录用日期:  2022-05-10
  • 出版日期:  2022-11-20
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