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细胞焦亡在非酒精性脂肪性肝病中的作用

尹静亚 杨冰清 李越

引用本文:
Citation:

细胞焦亡在非酒精性脂肪性肝病中的作用

DOI: 10.3969/j.issn.1001-5256.2023.01.027
基金项目: 

国家自然科学基金 82000555

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:尹静亚负责论文参考文献查阅及撰文;杨冰清参与论文修改;李越负责综述构架制订,论文审校及最后定稿。
详细信息
    通信作者:

    李越, liyuedl04@126.com (ORCID: 0000-0002-7412-7632)

Role of pyroptosis in nonalcoholic fatty liver disease

Research funding: 

National Natural Science Foundation of China 82000555

More Information
  • 摘要: 细胞焦亡作为一种新型的细胞死亡方式,在非酒精性脂肪性肝病(NAFLD)中扮演着重要角色,对细胞焦亡的研究有助于NAFLD治疗新靶点的挖掘。本文从细胞焦亡的研究背景及机制和细胞焦亡在NAFLD中的作用两方面对细胞焦亡的研究进展进行综述,尤其对GSDME、caspase-11等细胞焦亡执行分子,以及AIM2等既往关注较少的炎性小体的功能作用进行了阐释。

     

  • 图  1  细胞焦亡及其阻断剂在NAFLD中的调控机制示意图

    注:Apaf-1,凋亡酶激活因子-1;AIM2,一种DNA感受器;ASC,凋亡相关斑点样蛋白;DAMP,损伤相关分子模式;dsDNA,双链DNA;GSDMD-N,GSDMD的N端结构域;GSDME-N,GSDME的N端结构域;LPS,细菌脂多糖;MPT,线粒体通透性转换;MCP-1,单核细胞趋化蛋白-1;PAMP,病原相关分子模式;pro-caspase-1,前半胱天冬酶-1;TXNIP,硫氧还蛋白结合蛋白。虚线箭头:表示尚未有证据显示参与NAFLD的过程。

    Figure  1.  The regulatory mechanism diagram of pyroptosis and its blocker in NAFLD

    表  1  程序性死亡之间的区别

    Table  1.   The difference between procedural deaths

    类别 诱因 主要机制 细胞形态 细胞膜 细胞器 细胞核
    细胞焦亡 病理性或损伤性因素 caspase-1/4/5/11切割GSDMD在质膜成孔,导致细胞裂解 肿胀变形 破裂 变形 变化不明显
    细胞凋亡 生理条件下基因调控 由caspase-3/6/7/8/9/10等激活所介导细胞死亡 皱缩,可见凋亡小体 完好 完整 固缩
    细胞自噬 营养缺乏或应激 细胞形成自噬体包裹细胞内成分转移至溶酶体进行消化,使细胞死亡 内可见自噬泡 完好 被自噬体包裹后在溶酶体中消化 变化不明显
    坏死性凋亡 病理性或损伤性因素 外来刺激激活RIPK1-PIPK3-MLKL通路或PIPK3-MLKL通路,在质膜打孔导致细胞裂解 肿胀变形 破裂 肿胀 被分解
    铁死亡 铁和活性氧(ROS)蓄积 谷胱甘肽过氧化酶4受抑制或在二价铁和酯氧合酶作用下,脂质发生过氧化,诱导细胞死亡 内可见气球样
    表型
    破裂 线粒体体积减小、双层膜密度增加、外膜破裂、线粒体嵴消失 变化不明显
    NETosis 细菌、真菌感染 外界刺激诱导中性粒细胞内NE、MPO、PAD4等蛋白表达,促进胞质和细胞核成分融合,并随着细胞破裂在细胞外形成NET捕获网,以捕获和杀死病原体 有NET捕获网形成 破裂 被挤压成网状结构 核膜溶解,染色质和组蛋白形成NET捕获网
    下载: 导出CSV
  • [1] POWELL EE, WONG VW, RINELLA M. Non-alcoholic fatty liver disease[J]. Lancet, 2021, 397(10290): 2212-2224. DOI: 10.1016/S0140-6736(20)32511-3.
    [2] LI J, ZOU B, YEO YH, et al. Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999-2019: a systematic review and meta-analysis[J]. Lancet Gastroenterol Hepatol, 2019, 4(5): 389-398. DOI: 10.1016/S2468-1253(19)30039-1.
    [3] YAN J, XIE W, OU WN, et al. Epidemiological survey and risk factor analysis of fatty liver disease of adult residents, Beijing, China[J]. J Gastroenterol Hepatol, 2013, 28(10): 1654-1659. DOI: 10.1111/jgh.12290.
    [4] KUANG S, ZHENG J, YANG H, et al. Structure insight of GSDMD reveals the basis of GSDMD autoinhibition in cell pyroptosis[J]. Proc Natl Acad Sci U S A, 2017, 114(40): 10642-10647. DOI: 10.1073/pnas.1708194114.
    [5] XIAO WS, LE YY, ZENG SL, et al. Role of pyroptosis in liver diseases[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.
    [6] PUGLIESE N, PLAZ TORRES MC, PETTA S, et al. Is there an 'ideal' diet for patients with NAFLD?[J]. Eur J Clin Invest, 2022, 52(3): e13659. DOI: 10.1111/eci.13659.
    [7] BOISE LH, COLLINS CM. Salmonella-induced cell death: apoptosis, necrosis or programmed cell death?[J]. Trends Microbiol, 2001, 9(2): 64-67. DOI: 10.1016/s0966-842x(00)01937-5.
    [8] SHI J, ZHAO Y, WANG K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death[J]. Nature, 2015, 526(7575): 660-665. DOI: 10.1038/nature15514.
    [9] KAYAGAKI N, STOWE IB, LEE BL, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling[J]. Nature, 2015, 526(7575): 666-671. DOI: 10.1038/nature15541.
    [10] HIRSOVA P, GORES GJ. Death receptor-mediated cell death and proinflammatory signaling in nonalcoholic steatohepatitis[J]. Cell Mol Gastroenterol Hepatol, 2015, 1(1): 17-27. DOI: 10.1016/j.jcmgh.2014.11.005.
    [11] D'ARCY MS. Cell death: a review of the major forms of apoptosis, necrosis and autophagy[J]. Cell Biol Int, 2019, 43(6): 582-592. DOI: 10.1002/cbin.11137.
    [12] YAN J, WAN P, CHOKSI S, et al. Necroptosis and tumor progression[J]. Trends Cancer, 2022, 8(1): 21-27. DOI: 10.1016/j.trecan.2021.09.003.
    [13] BATTAGLIA AM, CHIRILLO R, AVERSA I, et al. Ferroptosis and cancer: Mitochondria meet the "iron maiden" cell death[J]. Cells, 2020, 9(6): 1505. DOI: 10.3390/cells9061505.
    [14] THIAM HR, WONG SL, WAGNER DD, et al. Cellular mechanisms of NETosis[J]. Annu Rev Cell Dev Biol, 2020, 36: 191-218. DOI: 10.1146/annurev-cellbio-020520-111016.
    [15] SARHAN J, LIU BC, MUENDLEIN HI, et al. Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during Yersinia infection[J]. Proc Natl Acad Sci U S A, 2018, 115(46): E10888-E10897. DOI: 10.1073/pnas.1809548115.
    [16] TANG R, XU J, ZHANG B, et al. Ferroptosis, necroptosis, and pyroptosis in anticancer immunity[J]. J Hematol Oncol, 2020, 13(1): 110. DOI: 10.1186/s13045-020-00946-7.
    [17] GAUTHERON J, GORES GJ, RODRIGUES C. Lytic cell death in metabolic liver disease[J]. J Hepatol, 2020, 73(2): 394-408. DOI: 10.1016/j.jhep.2020.04.001.
    [18] COLAK Y, HASAN B, ERKALMA B, et al. Pathogenetic mechanisms of nonalcoholic fatty liver disease and inhibition of the inflammasome as a new therapeutic target[J]. Clin Res Hepatol Gastroenterol, 2021, 45(4): 101710. DOI: 10.1016/j.clinre.2021.101710.
    [19] 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.
    [20] AL MAMUN A, WU Y, JIA C, et al. Role of pyroptosis in liver diseases[J]. Int Immunopharmacol, 2020, 84: 106489. DOI: 10.1016/j.intimp.2020.106489.
    [21] 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.
    [22] XU W, CHE Y, ZHANG Q, et al. Apaf-1 pyroptosome senses mitochondrial permeability transition[J]. Cell Metab, 2021, 33(2): 424-436. e10. DOI: 10.1016/j.cmet.2020.11.018.
    [23] 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.
    [24] ZHU Y, ZHAO H, LU J, et al. Caspase-11-mediated hepatocytic pyroptosis promotes the progression of nonalcoholic steatohepatitis[J]. Cell Mol Gastroenterol Hepatol, 2021, 12(2): 653-664. DOI: 10.1016/j.jcmgh.2021.04.009.
    [25] MITSUYOSHI H, YASUI K, HARA T, et al. Hepatic nucleotide binding oligomerization domain-like receptors pyrin domain-containing 3 inflammasomes are associated with the histologic severity of non-alcoholic fatty liver disease[J]. Hepatol Res, 2017, 47(13): 1459-1468. DOI: 10.1111/hepr.12883.
    [26] CSAK T, PILLAI A, GANZ M, et al. Both bone marrow-derived and non-bone marrow-derived cells contribute to AIM2 and NLRP3 inflammasome activation in a MyD88-dependent manner in dietary steatohepatitis[J]. Liver Int, 2014, 34(9): 1402-1413. DOI: 10.1111/liv.12537.
    [27] GONG Z, ZHANG X, SU K, et al. Deficiency in AIM2 induces inflammation and adipogenesis in white adipose tissue leading to obesity and insulin resistance[J]. Diabetologia, 2019, 62(12): 2325-2339. DOI: 10.1007/s00125-019-04983-x.
    [28] YU X, HAO M, LIU Y, et al. Liraglutide ameliorates non-alcoholic steatohepatitis by inhibiting NLRP3 inflammasome and pyroptosis activation via mitophagy[J]. Eur J Pharmacol, 2019, 864: 172715. DOI: 10.1016/j.ejphar.2019.172715.
    [29] MAI W, XU Y, XU J, et al. Berberine inhibits nod-like receptor family pyrin domain containing 3 inflammasome activation and pyroptosis in nonalcoholic steatohepatitis via the ROS/TXNIP axis[J]. Front Pharmacol, 2020, 11: 185. DOI: 10.3389/fphar.2020.00185.
    [30] RUAN S, HAN C, SHENG Y, et al. Antcin A alleviates pyroptosis and inflammatory response in Kupffercells of non-alcoholic fatty liver disease by targeting NLRP3[J]. Int Immunopharmacol, 2021, 100: 108126. DOI: 10.1016/j.intimp.2021.108126.
    [31] ZHU P, PENG Y, WU LL, et al. Research progress on the involvement of pyroptosis in nonalcoholic fatty liver disease[J]. Chin Hepatol, 2021, 26(11): 1290-1293. DOI: 10.14000/j.cnki.issn.1008-1704.2021.11.026.

    朱鹏, 彭旸, 吴莉莉, 等. 细胞焦亡参与非酒精性脂肪性肝病的相关研究进展[J]. 肝脏, 2021, 26(11): 1290-1293. DOI: 10.14000/j.cnki.issn.1008-1704.2021.11.026.
    [32] DEWIDAR B, MEYER C, DOOLEY S, et al. TGF-β in hepatic stellate cell activation and liver fibrogenesis-updated 2019[J]. Cells, 2019, 8(11): 1419. DOI: 10.3390/cells8111419.
    [33] WU J, LIN S, WAN B, et al. Pyroptosis in liver disease: New insights into disease mechanisms[J]. Aging Dis, 2019, 10(5): 1094-1108. DOI: 10.14336/AD.2019.0116.
    [34] INZAUGARAT ME, JOHNSON CD, HOLTMANN TM, et al. NLR family pyrin domain-containing 3 inflammasome activation in hepatic stellate cells induces liver fibrosis in mice[J]. Hepatology, 2019, 69(2): 845-859. DOI: 10.1002/hep.30252.
    [35] GAUL S, LESZCZYNSKA A, ALEGRE F, et al. Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis[J]. J Hepatol, 2021, 74(1): 156-167. DOI: 10.1016/j.jhep.2020.07.041.
    [36] GUO B, FU S, ZHANG J, et al. Targeting inflammasome/IL-1 pathways for cancer immunotherapy[J]. Sci Rep, 2016, 6: 36107. DOI: 10.1038/srep36107.
    [37] ZHANG X, LI C, CHEN D, et al. H. pylori CagA activates the NLRP3 inflammasome to promote gastric cancer cell migration and invasion[J]. Inflamm Res, 2022, 71(1): 141-155. DOI: 10.1007/s00011-021-01522-6.
    [38] GARCÍA-PRAS E, FERNÁNDEZ-IGLESIAS A, GRACIA-SANCHO J, et al. Cell death in hepatocellular carcinoma: Pathogenesis and therapeutic opportunities[J]. Cancers (Basel), 2021, 14(1): 48. DOI: 10.3390/cancers14010048.
    [39] YAN H, LUO B, WU X, et al. Cisplatin induces pyroptosis via activation of MEG3/NLRP3/caspase-1/GSDMD pathway in triple-negative breast cancer[J]. Int J Biol Sci, 2021, 17(10): 2606-2621. DOI: 10.7150/ijbs.60292.
    [40] ZHOU CB, FANG JY. The role of pyroptosis in gastrointestinal cancer and immune responses to intestinal microbial infection[J]. Biochim Biophys Acta Rev Cancer, 2019, 1872(1): 1-10. DOI: 10.1016/j.bbcan.2019.05.001.
    [41] HUANG DQ, EL-SERAG HB, LOOMBA R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(4): 223-238. DOI: 10.1038/s41575-020-00381-6.
    [42] CHEN YF, QI HY, WU FL. Euxanthone exhibits anti-proliferative and anti-invasive activities in hepatocellular carcinoma by inducing pyroptosis: preliminary results[J]. Eur Rev Med Pharmacol Sci, 2018, 22(23): 8186-8196. DOI: 10.26355/eurrev_201812_16511.
    [43] WEI Q, MU K, LI T, et al. Deregulation of the NLRP3 inflammasome in hepatic parenchymal cells during liver cancer progression[J]. Lab Invest, 2014, 94(1): 52-62. DOI: 10.1038/labinvest.2013.126.
    [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] ZHANG Y, YANG H, SUN M, et al. Alpinumisoflavone suppresses hepatocellular carcinoma cell growth and metastasis via NLRP3 inflammasome-mediated pyroptosis[J]. Pharmacol Rep, 2020, 72(5): 1370-1382. DOI: 10.1007/s43440-020-00064-8.
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  • 收稿日期:  2022-05-02
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  • 出版日期:  2023-01-20
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