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

巨噬细胞胞葬功能在急慢性肝病中的作用机制及其靶向治疗

杨焕焕 袁诗雨 唐映梅

引用本文:
Citation:

巨噬细胞胞葬功能在急慢性肝病中的作用机制及其靶向治疗

DOI: 10.12449/JCH240432
基金项目: 

国家自然科学基金 (82360108);

云南省医学领军人才项目 (L-2019013);

云南万人计划名医专项 (YNWR-MY-2018-028);

云南省科技人才与平台计划 (The Yunan Academician Expert Workstation 202305AF150065);

昆明医科大学第二附属医院临床研究项目 (2020ynlc010);

昆明医科大学第二附属医院临床研究项目 (ynIIT2021017)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:杨焕焕负责起草文章,对行文思路和设计有关键贡献;袁诗雨负责查阅及分析参考文献;唐映梅修改文章关键内容。
详细信息
    通信作者:

    唐映梅, tangyingmei_med@kmmu.edu.cn (ORCID: 0000-0002-0731-4198)

Mechanism of action of macrophage efferocytosis in acute and chronic liver diseases and related targeted therapy

Research funding: 

National Natural Science Foundation of China (82360108);

Medicine Leading Talents of Yunnan Province (L-2019013);

The Yunnan Wanren Project (YNWR-MY-2018-028);

Yunnan Province Science And Technology Talents and Platform Plan (The Yunan Academician Expert Workstation 202305AF150065);

Clinical Research Project of the Second Affiliated Hospital of Kunming Medical University (2020ynlc010);

Clinical Research Project of the Second Affiliated Hospital of Kunming Medical University (ynIIT2021017)

More Information
  • 摘要: 胞葬作用是指吞噬细胞(包括巨噬细胞、树突状细胞等专职吞噬细胞和上皮细胞等非专职吞噬细胞)吞噬并清除凋亡细胞的过程。肝巨噬细胞是肝脏中具有胞葬功能的主要细胞。近年来,越来越多的研究表明包括急性肝损伤、酒精性肝病、非酒精性脂肪性肝病、自身免疫性肝病、肝纤维化及肝细胞癌等在内的多种急慢性肝病均与肝巨噬细胞的胞葬作用有关。本文通过阐述巨噬细胞胞葬相关分子的表达、胞葬过程及其胞葬功能在不同肝病中作用的最新研究进展,旨在为肝病治疗提供新思路。

     

  • 表  1  凋亡细胞和巨噬细胞胞葬相关分子

    Table  1.   Funeral-related molecules in apoptotic cells and macrophages

    凋亡细胞胞葬配体 巨噬细胞胞葬受体 桥接分子
    LPC、S1P、ATP、UTP、PS 直接受体:G2A、S1PR、P2Y2、LRP1、SRB1、BAI1、TIM-4、RAGE、TREM2 间接受体:TAM、Integrins Gas6、ProS、MFGE8
    下载: 导出CSV
  • [1] RAZI S, YAGHMOORIAN KHOJINI J, KARGARIJAM F, et al. Macrophage efferocytosis in health and disease[J]. Cell Biochem Funct, 2023, 41( 2): 152- 165. DOI: 10.1002/cbf.3780.
    [2] DORAN AC, YURDAGUL A Jr, TABAS I. Efferocytosis in health and disease[J]. Nat Rev Immunol, 2020, 20( 4): 254- 267. DOI: 10.1038/s41577-019-0240-6.
    [3] ZHOU YX, YAO YH, DENG YC, et al. Regulation of efferocytosis as a novel cancer therapy[J]. Cell Commun Signal, 2020, 18( 1): 71. DOI: 10.1186/s12964-020-00542-9.
    [4] 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.
    [5] HORST AK, TIEGS G, DIEHL L. Contribution of macrophage efferocytosis to liver homeostasis and disease[J]. Front Immunol, 2019, 10: 2670. DOI: 10.3389/fimmu.2019.02670.
    [6] ZHANG YF, WANG YR, DING J, et al. Efferocytosis in multisystem diseases(Review)[J]. Mol Med Rep, 2022, 25( 1): 13. DOI: 10.3892/mmr.2021.12529.
    [7] BOADA-ROMERO E, MARTINEZ J, HECKMANN BL, et al. The clearance of dead cells by efferocytosis[J]. Nat Rev Mol Cell Biol, 2020, 21( 7): 398- 414. DOI: 10.1038/s41580-020-0232-1.
    [8] GE Y, HUANG M, YAO YM. Efferocytosis and its role in inflammatory disorders[J]. Front Cell Dev Biol, 2022, 10: 839248. DOI: 10.3389/fcell.2022.839248.
    [9] MORIOKA S, MAUERÖDER C, RAVICHANDRAN KS. Living on the edge: Efferocytosis at the interface of homeostasis and pathology[J]. Immunity, 2019, 50( 5): 1149- 1162. DOI: 10.1016/j.immuni.2019.04.018.
    [10] GHEIBI HAYAT SM, BIANCONI V, PIRRO M, et al. Efferocytosis: Molecular mechanisms and pathophysiological perspectives[J]. Immunol Cell Biol, 2019, 97( 2): 124- 133. DOI: 10.1111/imcb.12206.
    [11] ZHENG YF, CUI BP, SUN WR, et al. Potential crosstalk between liver and extra-liver organs in mouse models of acute liver injury[J]. Int J Biol Sci, 2020, 16( 7): 1166- 1179. DOI: 10.7150/ijbs.41293.
    [12] HUANG HT, JIANG JY, CHEN RH, et al. The role of macrophage TAM receptor family in the acute-to-chronic progression of liver disease: From friend to foe?[J]. Liver Int, 2022, 42( 12): 2620- 2631. DOI: 10.1111/liv.15380.
    [13] HU HR, CHENG XY, LI F, et al. Defective efferocytosis by aged macrophages promotes STING signaling mediated inflammatory liver injury[J]. Cell Death Discov, 2023, 9( 1): 236. DOI: 10.1038/s41420-023-01497-9.
    [14] NI M, ZHANG J, SOSA R, et al. T-cell immunoglobulin and mucin domain-containing protein-4 is critical for kupffer cell homeostatic function in the activation and resolution of liver ischemia reperfusion injury[J]. Hepatology, 2021, 74( 4): 2118- 2132. DOI: 10.1002/hep.31906.
    [15] HAN S, LI XD, XIA N, et al. Myeloid Trem2 dynamically regulates the induction and resolution of hepatic ischemia-reperfusion injury inflammation[J]. Int J Mol Sci, 2023, 24( 7): 6348. DOI: 10.3390/ijms24076348.
    [16] ZHANG LY, CHEN Q, SHI CX, et al. Research progress of autophagy on acute liver failure[J/OL]. Chin J Liver Dis Electron Version, 2022, 14( 4): 10- 14. DOI: 10.3969/j.issn.1674-7380.2022.04.002.

    张璐懿, 陈倩, 石春霞, 等. 自噬在急性肝衰竭中研究进展[J/OL]. 中国肝脏病杂志(电子版), 2022, 14( 4): 10- 14. DOI: 10.3969/j.issn.1674-7380.2022.04.002.
    [17] CAI BS, KASIKARA C, DORAN AC, et al. MerTK signaling in macrophages promotes the synthesis of inflammation resolution mediators by suppressing CaMKII activity[J]. Sci Signal, 2018, 11( 549): eaar3721. DOI: 10.1126/scisignal.aar3721.
    [18] TRIANTAFYLLOU E, POP OT, POSSAMAI LA, et al. MerTK expressing hepatic macrophages promote the resolution of inflammation in acute liver failure[J]. Gut, 2018, 67( 2): 333- 347. DOI: 10.1136/gutjnl-2016-313615.
    [19] LI Y, YANG S. Progress on alcoholic liver disease[J/OL]. Chin J Liver Dis Electron Version, 2022, 14( 3): 1- 4. DOI: 10.3969/j.issn.1674-7380.2022.03.001.

    李玥, 杨松. 酒精性肝病研究进展[J/OL]. 中国肝脏病杂志(电子版), 2022, 14( 3): 1- 4. DOI: 10.3969/j.issn.1674-7380.2022.03.001.
    [20] CHAUNG WW, BRENNER M, YEN HT, et al. Recombinant human milk fat globule-EGF factor VIII(rhMFG-E8) as a therapy for sepsis after acute exposure to alcohol[J]. Mol Med, 2019, 25( 1): 52. DOI: 10.1186/s10020-019-0118-x.
    [21] WANG X, BU HF, ZHONG W, et al. MFG-E8 and HMGB1 are involved in the mechanism underlying alcohol-induced impairment of macrophage efferocytosis[J]. Mol Med, 2013, 19( 1): 170- 182. DOI: 10.2119/molmed.2012.00260.
    [22] BUKONG TN, CHO Y, IRACHETA-VELLVE A, et al. Abnormal neutrophil traps and impaired efferocytosis contribute to liver injury and sepsis severity after binge alcohol use[J]. J Hepatol, 2018, 69( 5): 1145- 1154. DOI: 10.1016/j.jhep.2018.07.005.
    [23] WANG XJ, MALHI H. Nonalcoholic fatty liver disease[J]. Ann Intern Med, 2018, 169( 9): ITC65. DOI: 10.7326/aitc201811060.
    [24] WANG CE, XU WT, GONG J, et al. Advances in the treatment of nonalcoholic fatty liver disease[J]. Clin J Med Offic, 2022, 50( 9): 897- 899, 903. DOI: 10.16680/j.1671-3826.2022.09.06.

    王彩娥, 许文涛, 宫建, 等. 非酒精性脂肪性肝病治疗研究进展[J]. 临床军医杂志, 2022, 50( 9): 897- 899, 903. DOI: 10.16680/j.1671-3826.2022.09.06.
    [25] WANG XC, HE QF, ZHOU CL, et al. Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development[J]. Immunity, 2023, 56( 1): 58- 77. e 11. DOI: 10.1016/j.immuni.2022.11.013.
    [26] TRIVEDI PJ, HIRSCHFIELD GM. Recent advances in clinical practice: Epidemiology of autoimmune liver diseases[J]. Gut, 2021, 70( 10): 1989- 2003. DOI: 10.1136/gutjnl-2020-322362.
    [27] SHOJAIE L, IORGA A, DARA L. Cell death in liver diseases: A review[J]. Int J Mol Sci, 2020, 21( 24): 9682. DOI: 10.3390/ijms21249682.
    [28] QI N, LIU PP, ZHANG Y, et al. Development of a spontaneous liver disease resembling autoimmune hepatitis in mice lacking tyro3, axl and mer receptor tyrosine kinases[J]. PLoS One, 2013, 8( 6): e66604. DOI: 10.1371/journal.pone.0066604.
    [29] KAWANO M, NAGATA S. Efferocytosis and autoimmune disease[J]. Int Immunol, 2018, 30( 12): 551- 558. DOI: 10.1093/intimm/dxy055.
    [30] ROEHLEN N, CROUCHET E, BAUMERT TF. Liver fibrosis: Mechanistic concepts and therapeutic perspectives[J]. Cells, 2020, 9( 4): 875. DOI: 10.3390/cells9040875.
    [31] PASTORE M, CALIGIURI A, RAGGI C, et al. Macrophage MerTK promotes profibrogenic cross-talk with hepatic stellate cells via soluble mediators[J]. JHEP Rep, 2022, 4( 4): 100444. DOI: 10.1016/j.jhepr.2022.100444.
    [32] ANWANWAN D, SINGH SK, SINGH S, et al. Challenges in liver cancer and possible treatment approaches[J]. Biochim Biophys Acta Rev Cancer, 2020, 1873( 1): 188314. DOI: 10.1016/j.bbcan.2019.188314.
    [33] MEHROTRA P, RAVICHANDRAN KS. Drugging the efferocytosis process: Concepts and opportunities[J]. Nat Rev Drug Discov, 2022, 21( 8): 601- 620. DOI: 10.1038/s41573-022-00470-y.
    [34] HUELSE JM, FRIDLYAND DM, EARP S, et al. MERTK in cancer therapy: Targeting the receptor tyrosine kinase in tumor cells and the immune system[J]. Pharmacol Ther, 2020, 213: 107577. DOI: 10.1016/j.pharmthera.2020.107577.
    [35] ZHOU Y, FEI MJ, ZHANG G, et al. Blockade of the phagocytic receptor MerTK on tumor-associated macrophages enhances P2X7R-dependent STING activation by tumor-derived cGAMP[J]. Immunity, 2020, 52( 2): 357- 373. e 9. DOI: 10.1016/j.immuni.2020.01.014.
    [36] CHENG L, WENG BB, JIA CS, et al. The expression and significance of efferocytosis and immune checkpoint related molecules in pancancer samples and the correlation of their expression with anticancer drug sensitivity[J]. Front Pharmacol, 2022, 13: 977025. DOI: 10.3389/fphar.2022.977025.
  • 加载中
表(1)
计量
  • 文章访问数:  400
  • HTML全文浏览量:  329
  • PDF下载量:  36
  • 被引次数: 0
出版历程
  • 收稿日期:  2023-08-20
  • 录用日期:  2023-10-07
  • 出版日期:  2024-04-25
  • 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