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

doi:10.3969/j.issn.1001-5256.2022.11.035

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

湖南中医药大学第一附属医院肝病科，长沙 410007

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

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

Mechanism of NLRP3 inflammasome promoting hepatic stellate cell activation

Department of Hepatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410007, China

Research funding:

National Science Fund for Distinguished Young Scholar (81904182);

Natural Science Foundation of Hunan Province (S2020JJ5441)

More Information

Corresponding author: SUN Kewei, Keweisun@aliyun.com(ORCID: 0000-0002-9734-3717)

摘要

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。
- 肝硬化 /
- 肝星状细胞 /
- NLRP3炎症小体 /
- 炎症微环境
Abstract: Liver fibrosis is the common result of various chronic liver injuries and can progress to liver cirrhosis and even liver cancer, and at present, there is still no effective means to reverse liver fibrosis. The transformation of activated hepatic stellate cells (HSC) in perisinusoidal space into myofibroblasts and the secretion of collagen are a central event in the process of liver fibrosis. NLRP3 inflammasome can be activated by various injury stimuli and mediate inflammatory response and pyroptosis. Recent studies have found that the activation of NLRP3 inflammasome is closely associated with HSC activation. This article introduces the activation of NLRP3 inflammasome in different pathways in HSC under various pathological factors and role of NLRP3 inflammasome in the formation of extracellular inflammatory microenvironment, thereby mediating HSC activation and playing an important role in promoting liver fibrosis.
- Liver Cirrhosis /
- Hepatic Stellate Cells /
- NLRP3 Inflammasome /
- Inflammatory Microenvironment

HTML全文

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

下载: 全尺寸图片幻灯片

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

下载: 全尺寸图片幻灯片

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