中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

细胞焦亡的发生机制及其在肝脏疾病发生发展中的作用

王欣悦 李德冠

引用本文:
Citation:

细胞焦亡的发生机制及其在肝脏疾病发生发展中的作用

DOI: 10.3969/j.issn.1001-5256.2021.12.051
基金项目: 

国家自然科学基金 (81972975)

详细信息
    通信作者:

    李德冠,lideguan@irm-cams.ac.cn

  • 中图分类号: R575

Mechanism of pyroptosis and its role in the development and progression of liver diseases

Research funding: 

National Natural Science Foundation of China (81972975)

  • 摘要: 细胞焦亡是一种机体清除内源性和外源性伤害刺激的程序性细胞死亡方式。GSDMD和GSDME是细胞焦亡的主要执行者,属于Gasdermin蛋白家族,可被活化的caspases切割后在细胞膜上穿孔造成细胞内IL-18、IL-1β等炎性因子的释放,发生细胞焦亡。最近研究发现,细胞焦亡参与肝脏疾病的发生发展过程,并在其中发挥“双刃剑”的作用。阐述了细胞焦亡的分子机制以及细胞焦亡在肝脏疾病发生发展中的研究进展,从而为防治肝脏相关疾病提供新的靶点和思路。

     

  • 图  1  细胞焦亡示意图

    注:Death Receptor,死亡受体;Chemotherapy drugs,化疗药物;Virus,病毒;Toxins,毒素;Bacteria,细菌;Cytochrome c,线粒体细胞色素c;Apoptosis,细胞凋亡。

  • [1] ZYCHLINSKY A, PREVOST MC, SANSONETTI PJ. Shigella flexneri induces apoptosis in infected macrophages[J]. Nature, 1992, 358(6382): 167-169. DOI: 10.1038/358167a0.
    [2] de VASCONCELOS NM, van OPDENBOSCH N, van GORP H, et al. Single-cell analysis of pyroptosis dynamics reveals conserved GSDMD-mediated subcellular events that precede plasma membrane rupture[J]. Cell Death Differ, 2019, 26(1): 146-161. DOI: 10.1038/s41418-018-0106-7.
    [3] GALLUZZI L, VITALE I, AARONSON SA, et al. Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death 2018[J]. Cell Death Differ, 2018, 25(3): 486-541. DOI: 10.1038/s41418-017-0012-4.
    [4] WANG X, LIU K, GONG H, et al. Death by histone deacetylase inhibitor quisinostat in tongue squamous cell carcinoma via apoptosis, pyroptosis, and ferroptosis[J]. Toxicol Appl Pharmacol, 2021, 410: 115363. DOI: 10.1016/j.taap.2020.115363.
    [5] FANG Y, TIAN S, PAN Y, et al. Pyroptosis: A new frontier in cancer[J]. Biomed Pharmacother, 2020, 121: 109595. DOI: 10.1016/j.biopha.2019.109595.
    [6] JIANG M, QI L, LI L, et al. The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer[J]. Cell Death Discov, 2020, 6: 112. DOI: 10.1038/s41420-020-00349-0.
    [7] GONG T, LIU L, JIANG W, et al. DAMP-sensing receptors in sterile inflammation and inflammatory diseases[J]. Nat Rev Immunol, 2020, 20(2): 95-112. DOI: 10.1038/s41577-019-0215-7.
    [8] ORNING P, LIEN E, FITZGERALD KA. Gasdermins and their role in immunity and inflammation[J]. J Exp Med, 2019, 216(11): 2453-2465. DOI: 10.1084/jem.20190545.
    [9] TIAN DD, WANG M, LIU A, et al. Antidepressant effect of paeoniflorin is through inhibiting pyroptosis CASP-11/GSDMD pathway[J]. Mol Neurobiol, 2021, 58(2): 761-776. DOI: 10.1007/s12035-020-02144-5.
    [10] WANG K, SUN Q, ZHONG X, et al. Structural mechanism for GSDMD targeting by autoprocessed caspases in pyroptosis[J]. Cell, 2020, 180(5): 941-955. e20. DOI: 10.1016/j.cell.2020.02.002.
    [11] LIU X, LIEBERMAN J. A mechanistic understanding of pyroptosis: The fiery death triggered by invasive infection[J]. Adv Immunol, 2017, 135: 81-117. DOI: 10.1016/bs.ai.2017.02.002.
    [12] CHEN KW, DEMARCO B, BROZ P. Pannexin-1 promotes NLRP3 activation during apoptosis but is dispensable for canonical or noncanonical inflammasome activation[J]. Eur J Immunol, 2020, 50(2): 170-177. DOI: 10.1002/eji.201948254.
    [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. DOI: 10.1038/nature22393.
    [14] WANG SJ, XU MN, WANG JB. Research progress of gasdermin D and gasdermin E-mediated pyropto-sis in tumors[J]. Chin J Clin Pharmacol Ther, 2020, 25(3): 352-360. DOI: 10.12092/j.issn.1009-2501. 2020.03.017.

    王石健, 徐蒙娜, 汪佳兵. gasdermin D和gasdermin E介导的细胞焦亡在肿瘤中的研究进展[J]. 中国临床药理学与治疗学, 2020, 25(3): 352-360. DOI: 10.12092/j.issn.1009-2501. 2020.03.017.
    [15] de SCHUTTER E, ROELANDT R, RIQUET FB, et al. Punching holes in cellular membranes: Biology and evolution of gasdermins[J]. Trends Cell Biol, 2021, 31(6): 500-513. DOI: 10.1016/j.tcb.2021.03.004.
    [16] Erratum: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2020, 70(4): 313. DOI: 10.3322/caac.21609.
    [17] XIAO J, WANG F, WONG NK, et al. Global liver disease burdens and research trends: Analysis from a Chinese perspective[J]. J Hepatol, 2019, 71(1): 212-221. DOI: 10.1016/j.jhep.2019.03.004.
    [18] SPEARMAN CW, DUSHEIKO GM, HELLARD M, et al. Hepatitis C[J]. Lancet, 2019, 394(10207): 1451-1466. DOI: 10.1016/S0140-6736(19)32320-7.
    [19] NICOLINI LA, ORSI A, TATARELLI P, et al. A Global View to HBV chronic infection: Evolving strategies for diagnosis, treatment and prevention in immunocompetent individuals[J]. Int J Environ Res Public Health, 2019, 16(18): 3307. DOI: 10.3390/ijerph16183307.
    [20] XIE WH, DING J, XIE XX, et al. Hepatitis B virus X protein promotes liver cell pyroptosis under oxidative stress through NLRP3 inflammasome activation[J]. Inflamm Res, 2020, 69(7): 683-696. DOI: 10.1007/s00011-020-01351-z.
    [21] MOLYVDAS A, GEORGOPOULOU U, LAZARIDIS N, et al. The role of the NLRP3 inflammasome and the activation of IL-1beta in the pathogenesis of chronic viral hepatic inflammation[J]. Cytokine, 2018, 110: 389-396. DOI: 10.1016/j.cyto.2018.04.032.
    [22] CHEN H, HE G, CHEN Y, et al. Differential activation of NLRP3, AIM2, and IFI16 inflammasomes in humans with acute and chronic hepatitis B[J]. Viral Immunol, 2018, 31(9): 639-645. DOI: 10.1089/vim.2018.0058.
    [23] KOFAHI HM, TAYLOR NG, HIRASAWA K, et al. Hepatitis C virus infection of cultured human hepatoma cells causes apoptosis and pyroptosis in both infected and bystander cells[J]. Sci Rep, 2016, 6: 37433. DOI: 10.1038/srep37433.
    [24] LUAN J, JU D. Inflammasome: A double-edged sword in liver diseases[J]. Front Immunol, 2018, 9: 2201. DOI: 10.3389/fimmu.2018.02201.
    [25] ALHETHEEL A, ALBARRAG A, HAKAMI A, et al. In the peripheral blood mononuclear cells (PBMCs) of HCV infected patients the expression of STAT1 and IRF-1 is downregulated while that of caspase-3 upregulated[J]. Acta Virol, 2020, 64(3): 352-358. DOI: 10.4149/av_2020_313.
    [26] KAI J, YANG X, WANG Z, et al. Oroxylin a promotes PGC-1α/Mfn2 signaling to attenuate hepatocyte pyroptosis via blocking mitochondrial ROS in alcoholic liver disease[J]. Free Radic Biol Med, 2020, 153: 89-102. DOI: 10.1016/j.freeradbiomed.2020.03.031.
    [27] XIAO WS, LE YY, ZENG SL, et al. The role of cell pyrotosis in liver disease[J]. J Clin Hepatol, 2020, 36(12): 2847-2850. DOI: 10.3969/j.issn.1001-5256.2020.12.044.

    肖伟松, 乐滢玉, 曾胜澜, 等. 细胞焦亡在肝脏疾病中的作用[J]. 临床肝胆病杂志, 2020, 36(12): 2847-2850. DOI: 10.3969/j.issn.1001-5256.2020.12.044.
    [28] HEO MJ, KIM TH, YOU JS, et al. Alcohol dysregulates miR-148a in hepatocytes through FoxO1, facilitating pyroptosis via TXNIP overexpression[J]. Gut, 2019, 68(4): 708-720. DOI: 10.1136/gutjnl-2017-315123.
    [29] 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. DOI: 10.1002/hep.29645.
    [30] MA HY, YAMAMOTO G, XU J, et al. IL-17 signaling in steatotic hepatocytes and macrophages promotes hepatocellular carcinoma in alcohol-related liver disease[J]. J Hepatol, 2020, 72(5): 946-959. DOI: 10.1016/j.jhep.2019.12.016.
    [31] MIYATA T, NAGY LE. Programmed cell death in alcohol-associated liver disease[J]. Clin Mol Hepatol, 2020, 26(4): 618-625. DOI: 10.3350/cmh.2020.0142.
    [32] WANG S, QING DX. Progress in inflammasome activation and pyrolysis in alcoholic liver disease[J]. J Cent South Univ(Med Sci), 2020, 45(8): 999-1004. DOI: 10.11817/j.issn.1672-7347.2020.190272.

    王烁, 卿笃信. 炎性小体激活与细胞焦亡及其在酒精性肝病中的研究进展[J]. 中南大学学报(医学版), 2020, 45(8): 999-1004. DOI: 10.11817/j.issn.1672-7347.2020.190272.
    [33] YOUNOSSI Z, ANSTEE QM, MARIETTI M, et al. Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(1): 11-20. DOI: 10.1038/nrgastro.2017.109.
    [34] IOANNOU GN, SUBRAMANIAN S, CHAIT A, et al. Cholesterol crystallization within hepatocyte lipid droplets and its role in murine NASH[J]. J Lipid Res, 2017, 58(6): 1067-1079. DOI: 10.1194/jlr.M072454.
    [35] KOH EH, YOON JE, KO MS, et al. Sphingomyelin synthase 1 mediates hepatocyte pyroptosis to trigger non-alcoholic steatohepatitis[J]. Gut, 2021, 70(10): 1954-1964. DOI: 10.1136/gutjnl-2020-322509.
    [36] XU B, JIANG M, CHU Y, et al. Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice[J]. J Hepatol, 2018, 68(4): 773-782. DOI: 10.1016/j.jhep.2017.11.040.
    [37] YANG R, TONNESSEEN TI. DAMPs and sterile inflammation in drug hepatotoxicity[J]. Hepatol Int, 2019, 13(1): 42-50. DOI: 10.1007/s12072-018-9911-9.
    [38] JAESCHKE H, RAMACHANDRAN A, CHAO X, et al. Emerging and established modes of cell death during acetaminophen-induced liver injury[J]. Arch Toxicol, 2019, 93(12): 3491-3502. DOI: 10.1007/s00204-019-02597-1.
    [39] IMAEDA AB, WATANABE A, SOHAIL MA, et al. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome[J]. J Clin Invest, 2009, 119(2): 305-314. DOI: 10.1172/JCI35958.
    [40] XU Y, WANG J, SONG X, et al. RIP3 induces ischemic neuronal DNA degradation and programmed necrosis in rat via AIF[J]. Sci Rep, 2016, 6: 29362. DOI: 10.1038/srep29362.
    [41] IORGA A, DARA L. Cell death in drug-induced liver injury[J]. Adv Pharmacol, 2019, 85: 31-74. DOI: 10.1016/bs.apha.2019.01.006.
    [42] CHEN Z, HE M, CHEN J, et al. Long non-coding RNA SNHG7 inhibits NLRP3-dependent pyroptosis by targeting the miR-34a/SIRT1 axis in liver cancer[J]. Oncol Lett, 2020, 20(1): 893-901. DOI: 10.3892/ol.2020.11635.
    [43] GUO H, XIE M, ZHOU C, et al. The relevance of pyroptosis in the pathogenesis of liver diseases[J]. Life Sci, 2019, 223: 69-73. DOI: 10.1016/j.lfs.2019.02.060.
    [44] 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. DOI: 10.3727/096504018X15462920753012.
    [45] LOZANO-RUIZ B, GONZÁLEZ-NAVAJAS JM. The emerging relevance of AIM2 in liver disease[J]. Int J Mol Sci, 2020, 21(18): 6535. DOI: 10.3390/ijms21186535.
    [46] WANG W, ZHU M, XU Z, et al. Ropivacaine promotes apoptosis of hepatocellular carcinoma cells through damaging mitochondria and activating caspase-3 activity[J]. Biol Res, 2019, 52(1): 36. DOI: 10.1186/s40659-019-0242-7.
    [47] WANG CJ, TANG L, SHEN DW, et al. The expression and regulation of DFNA5 in human hepatocellular carcinoma DFNA5 in hepatocellular carcinoma[J]. Mol Biol Rep, 2013, 40(12): 6525-6531. DOI: 10.1007/s11033-013-2581-8.
    [48] LIANG WF, GONG YX, LI HF, et al. Curcumin activates ROS signaling to promote pyroptosis in hepatocellular carcinoma HepG2 cells[J]. In Vivo, 2021, 35(1): 249-257. DOI: 10.21873/invivo.12253.
    [49] HAGE C, HOVES S, STRAUSS L, et al. Sorafenib induces pyroptosis in macrophages and triggers natural killer cell-mediated cytotoxicity against hepatocellular carcinoma[J]. Hepatology, 2019, 70(4): 1280-1297. DOI: 10.1002/hep.30666.
    [50] ZHANG X, ZHANG P, AN L, et al. Miltirone induces cell death in hepatocellular carcinoma cell through GSDME-dependent pyroptosis[J]. Acta Pharm Sin B, 2020, 10(8): 1397-1413. DOI: 10.1016/j.apsb.2020.06.015.
  • 加载中
图(1)
计量
  • 文章访问数:  516
  • HTML全文浏览量:  254
  • PDF下载量:  56
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-04-16
  • 录用日期:  2021-06-24
  • 出版日期:  2021-12-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回