消皮素D在肝脏疾病病理进展中的作用
DOI: 10.3969/j.issn.1001-5256.2023.03.035
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:桂雄斌、王明刚负责对研究思路的设计,李飞燕负责查阅相关文献,资料归纳、分析,撰写论文;毛德文负责指导修改论文及最后定稿。
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摘要: 消皮素D(GSDMD)在免疫炎症反应效能放大及细胞焦亡过程中扮演重要角色。其被caspase-1切割活化后,GSDMD-N端快速释放,锚定在细胞膜上并形成孔隙,随即引发细胞焦亡,同时伴随强促炎因子IL-1β和IL-18大量释放。急/慢性肝脏炎症反应、细胞死亡是病毒性肝炎、酒精性肝病、非酒精性脂肪性肝病、自身免疫性肝病、肝衰竭及肝细胞癌等肝脏疾病的共有病理特征。本文在概述GSDMD基本结构特点后,详细分析了其在多种肝脏疾病病理进展所扮演的重要角色。此外,提出了针对GSDMD为潜在治疗靶点的防治策略,可为肝脏疾病临床防治下一步研究的重点方向提供新的思路。Abstract: As a novel star molecule, gasdermin D (GSDMD) plays an important role in the amplification of immune inflammatory response and the process of pyroptosis. After being cleaved and activated by caspase-1, the N-terminal of GSDMD is rapidly released, which anchors on the cell membrane and forms pores, thereby leading to pyroptosis, accompanied by the release of a large amount of the strong proinflammatory factors IL-1β and IL-18. Acute/chronic liver inflammatory response and cell death are the common pathological features of liver diseases such as viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune liver disease, liver failure, and hepatocellular carcinoma. This article summarizes the basic structural characteristics of GSDMD and elaborates on its important role in the pathological progression of various liver diseases. In addition, it is proposed that prevention and treatment strategies with GSDMD as a potential therapeutic target can provide new ideas for further studies on the clinical prevention and treatment of liver diseases.
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Key words:
- Liver Diseases /
- Gasdermin D /
- Pathologic Processes /
- Cell Death
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[1] FRICKER M, TOLKOVSKY AM, BORUTAITE V, et al. Neuronal cell death[J]. Physiol Rev, 2018, 98(2): 813-880. DOI: 10.1152/physrev.00011.2017. [2] KARMAKAR M, MINNS M, GREENBERG EN, et al. N-GSDMD trafficking to neutrophil organelles facilitates IL-1β release independently of plasma membrane pores and pyroptosis[J]. Nat Commun, 2020, 11(1): 2212. DOI: 10.1038/s41467-020-16043-9. [3] FRANK D, VINCE JE. Pyroptosis versus necroptosis: similarities, differences, and crosstalk[J]. Cell Death Differ, 2019, 26(1): 99-114. DOI: 10.1038/s41418-018-0212-6. [4] YU P, ZHANG X, LIU N, et al. Pyroptosis: mechanisms and diseases[J]. Signal Transduct Target Ther, 2021, 6(1): 128. DOI: 10.1038/s41392-021-00507-5. [5] 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. [6] 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. [7] RODRÍGUEZ-ANTONIO I, LÓPEZ-SÁNCHEZ GN, URIBE M, et al. Role of the inflammasome, gasdermin D, and pyroptosis in non-alcoholic fatty liver disease[J]. J Gastroenterol Hepatol, 2021, 36(10): 2720-2727. DOI: 10.1111/jgh.15561. [8] 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. [9] ZENG DY, LI JM, LIN S, et al. Global burden of acute viral hepatitis and its association with socioeconomic development status, 1990-2019[J]. J Hepatol, 2021, 75(3): 547-556. DOI: 10.1016/j.jhep.2021.04.035. [10] SETO MT, CHEUNG KW, HUNG I. Management of viral hepatitis A, C, D and E in pregnancy[J]. Best Pract Res Clin Obstet Gynaecol, 2020, 68: 44-53. DOI: 10.1016/j.bpobgyn.2020.03.009. [11] CASTANEDA D, GONZALEZ AJ, ALOMARI M, et al. From hepatitis A to E: A critical review of viral hepatitis[J]. World J Gastroenterol, 2021, 27(16): 1691-1715. DOI: 10.3748/wjg.v27.i16.1691. [12] ZHENG M, WILLIAMS EP, MALIREDDI R, et al. Impaired NLRP3 inflammasome activation/pyroptosis leads to robust inflammatory cell death via caspase-8/RIPK3 during coronavirus infection[J]. J Biol Chem, 2020, 295(41): 14040-14052. DOI: 10.1074/jbc.RA120.015036. [13] AVILA MA, DUFOUR JF, GERBES AL, et al. Recent advances in alcohol-related liver disease (ALD): summary of a Gut round table meeting[J]. Gut, 2020, 69(4): 764-780. DOI: 10.1136/gutjnl-2019-319720. [14] SEITZ HK, BATALLER R, CORTEZ-PINTO H, et al. Alcoholic liver disease[J]. Nat Rev Dis Primers, 2018, 4(1): 16. DOI: 10.1038/s41572-018-0014-7. [15] AXLEY PD, RICHARDSON CT, SINGAL AK. Epidemiology of alcohol consumption and societal burden of alcoholism and alcoholic liver disease[J]. Clin Liver Dis, 2019, 23(1): 39-50. DOI: 10.1016/j.cld.2018.09.011. [16] CUI K, YAN G, XU C, et al. Invariant NKT cells promote alcohol-induced steatohepatitis through interleukin-1β in mice[J]. J Hepatol, 2015, 62(6): 1311-1318. DOI: 10.1016/j.jhep.2014.12.027. [17] 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. [18] KUMAR S, DUAN Q, WU R, et al. Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis[J]. Adv Drug Deliv Rev, 2021, 176: 113869. DOI: 10.1016/j.addr.2021.113869. [19] WANG XJ, MALHI H. Nonalcoholic fatty liver disease[J]. Ann Intern Med, 2018, 169(9): ITC65-ITC80. DOI: 10.7326/AITC201811060. [20] 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. [21] 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. [22] MANNE V, HANDA P, KOWDLEY KV. Pathophysiology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis[J]. Clin Liver Dis, 2018, 22(1): 23-37. DOI: 10.1016/j.cld.2017.08.007. [23] WREE A, MCGEOUGH MD, PEÑA CA, et al. NLRP3 inflammasome activation is required for fibrosis development in NAFLD[J]. J Mol Med (Berl), 2014, 92(10): 1069-1082. DOI: 10.1007/s00109-014-1170-1. [24] 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. [25] CHEN S, CAI X, LIU Y, et al. The macrophage-associated microRNA-4715-3p/Gasdermin D axis potentially indicates fibrosis progression in nonalcoholic fatty liver disease: evidence from transcriptome and biological data[J]. Bioengineered, 2022, 13(5): 11740-11751. DOI: 10.1080/21655979.2022.2072602. [26] BURDETTE BE, ESPARZA AN, ZHU H, et al. Gasdermin D in pyroptosis[J]. Acta Pharm Sin B, 2021, 11(9): 2768-2782. DOI: 10.1016/j.apsb.2021.02.006. [27] FLOREANI A, de MARTIN S, SECCHI MF, et al. Extrahepatic autoimmunity in autoimmune liver disease[J]. Eur J Intern Med, 2019, 59: 1-7. DOI: 10.1016/j.ejim.2018.10.014. [28] SUCHER E, SUCHER R, GRADISTANAC T, et al. Autoimmune hepatitis-immunologically triggered liver pathogenesis-diagnostic and therapeutic strategies[J]. J Immunol Res, 2019, 2019: 9437043. DOI: 10.1155/2019/9437043. [29] LUAN J, ZHANG X, WANG S, et al. NOD-like receptor protein 3 inflammasome-dependent IL-1β accelerated conA-induced hepatitis[J]. Front Immunol, 2018, 9: 758. DOI: 10.3389/fimmu.2018.00758. [30] HUMPHRIES F, SHMUEL-GALIA L, KETELUT-CARNEIRO N, et al. Succination inactivates gasdermin D and blocks pyroptosis[J]. Science, 2020, 369(6511): 1633-1637. DOI: 10.1126/science.abb9818. [31] CASTILLO-DELA CRUZ P, WANEK AG, KUMAR P, et al. Intestinal IL-17R signaling constrains IL-18-Driven liver inflammation by the regulation of microbiome-derived products[J]. Cell Rep, 2019, 29(8): 2270-2283. e7. DOI: 10.1016/j.celrep.2019.10.042. [32] ARROYO V, MOREAU R, JALAN R. Acute-on-chronic liver failure[J]. N Engl J Med, 2020, 382(22): 2137-2145. DOI: 10.1056/NEJMra1914900. [33] KARVELLAS CJ, FRANCOZ C, WEISS E. Liver transplantation in acute-on-chronic liver failure[J]. Transplantation, 2021, 105(7): 1471-1481. DOI: 10.1097/TP.0000000000003550. [34] LI H, ZHAO XK, CHENG YJ, et al. Gasdermin D-mediated hepatocyte pyroptosis expands inflammatory responses that aggravate acute liver failure by upregulating monocyte chemotactic protein 1/CC chemokine receptor-2 to recruit macrophages[J]. World J Gastroenterol, 2019, 25(44): 6527-6540. DOI: 10.3748/wjg.v25.i44.6527. [35] WU YL. The role of Gasdermin D inhibitor necrosulfonamide in acute liver failure[D]. Fuzhou: Fujian Medical University, 2020. DOI: 10.27020/d.cnki.gfjyu.2020.001021" target="_blank"> 10.27020/d.cnki.gfjyu.2020.001021 .吴奕隆. Gasdermin D抑制剂necrosulfonamide在急性肝衰竭中作用[D]. 福州: 福建医科大学, 2020. DOI: 10.27020/d.cnki.gfjyu.2020.001021" target="_blank">10.27020/d.cnki.gfjyu.2020.001021 .[36] YU LX, SCHWABE RF. The gut microbiome and liver cancer: mechanisms and clinical translation[J]. Nat Rev Gastroenterol Hepatol, 2017, 14(9): 527-539. DOI: 10.1038/nrgastro.2017.72. [37] GALICIA-MORENO M, SILVA-GOMEZ JA, LUCANO-LANDEROS S, et al. Liver Cancer: therapeutic challenges and the importance of experimental models[J]. Can J Gastroenterol Hepatol, 2021, 2021: 8837811. DOI: 10.1155/2021/8837811. [38] FU J, WANG H. Precision diagnosis and treatment of liver cancer in China[J]. Cancer Lett, 2018, 412: 283-288. DOI: 10.1016/j.canlet.2017.10.008. [39] 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. [40] LIU X, XIA S, ZHANG Z, et al. Channelling inflammation: gasdermins in physiology and disease[J]. Nat Rev Drug Discov, 2021, 20(5): 384-405. DOI: 10.1038/s41573-021-00154-z.
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