细胞焦亡在肝脏疾病中的作用

肖伟松; 乐滢玉; 曾胜澜; 覃小宾; 吴聪; 牙程玉; 毛德文

doi:10.3969/j.issn.1001-5256.2020.12.044

细胞焦亡在肝脏疾病中的作用

DOI: 10.3969/j.issn.1001-5256.2020.12.044

1. 广西中医药大学研究生学院
2. 广西中医药大学第一附属医院肝病一区

基金项目:

国家自然科学基金面上项目（81774236）;国家自然科学基金（81460718）;国家自然科学基金（81960841）；广西研究生教育创新计划资助项目（YCSY2019006）；

详细信息

中图分类号: R575
计量
- 文章访问数: 1199
- HTML全文浏览量: 84
- PDF下载量: 146
- 被引次数: 0
出版历程
- 收稿日期: 2020-06-19
- 出版日期: 2020-12-20

Role of pyroptosis in liver diseases

Graduate School,Guangxi University of Chinese Medicine
First Ward of Liver Diseases,The First Affiliated Hospital of Guangxi University of Chinese Medicine

Research funding:

摘要

摘要:
细胞焦亡是近年来发现的一种不同于细胞坏死、凋亡、自噬的细胞程序性死亡的新形式,其特征是在Gasdermin介导下,细胞膜发生破裂,并释放细胞内容物和促炎因子,进而导致细胞死亡。细胞焦亡信号通路分为依赖于半胱氨酸天冬氨酸酶-1（caspase-1）的经典型途径和依赖于caspase-4、5、11的非经典型途径,其中经典型途径中caspase-1的激活依赖于炎性小体发挥作用,非经典型途径则是直接激活caspase-4、5、11,最终导致gasdermin D（GSDMD）蛋白裂解,诱导膜孔隙的形成,IL-1β、IL-18成熟及释放,细胞膜破裂而发生焦亡。而最新研究表明,细胞焦亡参与慢性肝脏疾病患者的发生发展过程,并在其中发挥重要作用。因此,着重介绍了细胞焦亡的机制,归纳总结了细胞焦亡在非酒精性脂肪性肝病、酒精性肝病、病毒性肝炎、肝硬化、肝细胞癌发生、发展中作用的研究进展,以期为临床肝病的防治提供新思路和新方法。
- 细胞焦亡 /
- 肝疾病 /
- 炎性体 /
- 病理过程
Abstract:
As a novel form of programmed cell death different from cell necrosis,apoptosis,and autophagy discovered in recent years,pyroptosis is characterized by cell membrane rupture and release of cell contents and proinflammatory factors mediated by gasdermin,thus leading to cell death. Pyroptosis signaling pathways can be classified into classical pathways dependent on caspase-1 and non-classical pathways dependent on caspase-4/5/11; the activation of caspase-1 in classical pathways depends on the function of inflammasome,while the direct activation of caspase-4/5/11 is observed in non-classical pathways,which leads to the lysis of gasdermin D and induce the formation of membrane pores,the maturation and release of interleukin-1β and interleukin-18,and the rupture of cell membrane to cause pyroptosis. Latest research has shown that pyroptosis plays an important role in the development and progression of chronic liver diseases. This article introduces the mechanism of pyroptosis and summarizes the role of pyroptosis in the development and progression of nonalcoholic fatty liver disease,alcoholic liver disease,viral hepatitis,liver cirrhosis,and hepatocellular carcinoma,in order to provide new ideas and methods for the prevention and treatment of liver diseases in clinical practice.
- pyroptosis /
- liver disease /
- inflammasome /
- pathologic processes

HTML全文

参考文献(29)

[1] WREE A,HOLTMANN TM,INZAUGARAT ME,et al. Novel drivers of the inflammatory response in liver injury and fibrosis[J]. Semin Liver Dis,2019,39(3):275-282.

[2] CHEN Q,SHI P,WANG Y,et al. GSDMB promotes non-canonical pyroptosis by enhancing caspase-4 activity[J]. J Mol Cell Biol,2019,11(6):496-508.

[3] HUANG X,FENG Y,XIONG G,et al. Caspase-11,a specific sensor for intracellular lipopolysaccharide recognition,mediates the non-canonical inflammatory pathway of pyroptosis[J]. Cell Biosci,2019,9:31.

[4] AMARANTE-MENDES GP,ADJEMIAN S,BRANCO LM,et al. Pattern recognition receptors and the host cell death molecular machinery[J]. Front Immunol,2018,9:2379.

[5] MAN S,KARKI R,KANNEGANTI T. Molecular mechanisms and functions of pyroptosis,inflammatory caspases and inflammasomes in infectious diseases[J]. Immunol Rev,2017,277(1):61-75.

[6] HE Y,HARA H,NU'EZ G. Mechanism and regulation of NLRP3 inflammasome activation[J]. Trends Biochem Sci,2016,41(12):1012-1021.

[7] XIA X,WANG X,ZHENG Y,et al. What role does pyroptosis play in microbial infection?[J]. J Cell Physiol,2019,234(6):7885-7892.

[8] KAYAGAKI N,WARMING S,LAMKANFI M,et al. Non-canonical inflammasome activation targets caspase-11[J]. Nature,2011,479(7371):117-121.

[9] HE YUAN,HARA HIDEKI,NUNEZ G. Mechanism and regulation of NLRP3 inflammasome activation[J]. Trends Biochem Sci,2016,41:1012-1021.

[10] SAVIO L,de ANDRADE MELLO P,DA SILVA CG,et al. The P2X7 receptor in inflammatory diseases:Angel or demon?[J]. Front Pharmacol,2018,9:52.

[11] DING J,SHAO F. Growing a gasdermin pore in membranes of pyroptotic cells[J]. EMBO J,2018,37(15):e100067.

[12] YANG D,HE Y,MUN¨OZ-PLANILLO R,et al. Caspase-11requires the pannexin-1 channel and the purinergic P2X7pore to mediate pyroptosis and endotoxic shock[J]. Immunity,2015,43(5):923-932.

[13] WANG Y,GAO W,SHI X,et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin[J].Nature,2017,547(7661):99-103.

[14] KHANOVA E,WU R,WANG W,et al. Pyroptosis by caspase11/4-gasdermin-D pathway in alcoholic hepatitis in mice and patients[J]. Hepatology,2018,67(5):1737-1753.

[15] CUI K,YAN G,XU C,et al. Invariant NKT cells promote alcohol-induced steatohepatitis through interleukin-1βin mice[J]. J Hepatol,2015,62(6):1311-1318.

[16] HEO MJ,KIM TH,YOU JS,et al. Alcohol dysregulates miR-148a in hepatocytes through Fox O1,facilitating pyroptosis via TXNIP overexpression[J]. Gut,2019,68(4):708-720.

[17] SHI C,XUE W,HAN B,et al. Acetaminophen aggravates fat accumulation in NAFLD by inhibiting autophagy via the AMPK/m TOR pathway[J]. Eur J Pharmacol,2019,850:15-22.

[18] LV Y,GAO X,LUO Y,et al. Apigenin ameliorates HFD-induced NAFLD through regulation of the XO/NLRP3 pathways[J]. J Nutr Biochem,2019,71:110-121.

[19] MITSUYOSHI H,YASUI K,HARA T,et al. Hepatic nucleotide binding oligomerization domain-like receptors pyrin domaincontaining 3 inflammasomes are associated with the histologic severity of non-alcoholic fatty liver disease[J]. Hepatol Res,2017,47(13):1459-1468.

[20] ZHENG T,YANG X,LI W,et al. Salidroside attenuates highfat diet-induced nonalcoholic fatty liver disease via AMPKdependent TXNIP/NLRP3 pathway[J]. Oxid Med Cell Longev,2018,2018:8597897.

[21] MOLYVDAS A,GEORGOPOULOU U,LAZARIDIS N,et al. The role of the NLRP3 inflammasome and the activation of IL-1βin the pathogenesis of chronic viral hepatic inflammation[J]. Cytokine,2018,110:389-396.

[22] LUAN J,JU D. Inflammasome:A double-edged sword in liver diseases[J]. Front Immunol,2018,9:2201.

[23] INZAUGARAT ME,JOHNSON CD,HOLTMANN TM,et al. NLR family pyrin domain-containing 3 inflammasome activation in hepatic stel ate cells induces liver fibrosis in mice[J]. Hepatology,2019,69(2):845-859.

[24] MRIDHA AR,WREE A,ROBERTSON A,et al. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice[J]. J Hepatol,2017,66(5):1037-1046.

[25] YOU Y,HUANG Y,WANG D,et al. Angiotensin(1-7)inhibits arecoline-induced migration and collagen synthesis in human oral myofibroblasts via inhibiting NLRP3 inflammasome activation[J]. J Cell Physiol,2019,234(4):4668-4680.

[26] ZHENG H,WANG X,ZHANG Y,et al. Pien-Tze-Huang ameliorates hepatic fibrosis via suppressing NF-κB pathway and promoting HSC apoptosis[J]. J Ethnopharmacol,2019,244:111856.

[27] XIA X,WANG X,CHENG Z,et al. The role of pyroptosis in cancer:Pro-cancer or pro-“host”?[J]. Cell Death Dis,2019,10(9):650.

[28] WEI Q,ZHU R,ZHU J,et al. E2-induced activation of the NLRP3 inflammasome triggers pyroptosis and inhibits autophagy in HCC cells[J]. Oncol Res,2019,27(7):827-834.

[29] MA X,GUO P,QIU Y,et al. Loss of AIM2 expression promotes hepatocarcinoma progression through activation of m TOR-S6K1 pathway[J]. Oncotarget,2016,7(24):36185-36197.

施引文献

资源附件(0)

访问统计