巨噬细胞极化在肝纤维化中的调控作用机制

白小洋; 张旭; 海龙; 丁向春

doi:10.12449/JCH240329

巨噬细胞极化在肝纤维化中的调控作用机制

DOI: 10.12449/JCH240329

白小洋^{1a, 1b, 2},
张旭^1b,
海龙^1a,
丁向春^1a, , ,

1a.
宁夏医科大学总医院感染科，银川 750000
1b.
宁夏医科大学总医院医学科学研究院外科学研究室，银川 750000
2.
宁夏医科大学临床医学院，银川 750000

基金项目:

宁夏自然科学基金项目 (2023AAC03584);

宁夏自然科学基金项目 (2023AAC03519)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：白小洋负责撰写与修改论文；海龙参与查阅相关文献；丁向春、张旭负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
丁向春， 13619511758@163.com （ORCID： 0000-0003-0283-9419）

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- 被引次数: 0
出版历程
- 收稿日期: 2023-08-10
- 录用日期: 2023-11-10
- 出版日期: 2024-03-20

Regulatory effect and mechanism of macrophage polarization in liver fibrosis

Xiaoyang BAI^{1a, 1b, 2},
Xu ZHANG^1b,
Long HAI^1a,
Xiangchun DING^{1a
, ,
,}

1a.
Department of Infectious Diseases，Academy of Medical Sciences，General Hospital of Ningxia Medical University，Yinchuan 750000，China
1b.
Department of Surgery，Academy of Medical Sciences，General Hospital of Ningxia Medical University，Yinchuan 750000，China
2.
School of Clinical Medicine，Ningxia Medical University，Yinchuan 750000，China

Research funding:

Ningxia Natural Science Foundation (2023AAC03584);

Ningxia Natural Science Foundation (2023AAC03519)

More Information

Corresponding author: DING Xiangchun， 13619511758@163.com （ORCID： 0000-0003-0283-9419）

摘要

摘要: 肝纤维化是一种由病毒感染、酒精、化学物质等原因导致的慢性肝损伤的愈合反应，是慢性肝脏疾病进展为肝硬化和肝癌的关键环节。肝巨噬细胞被认为是肝损伤和修复的重要介质，巨噬细胞极化趋向对肝纤维化具有双向调控作用。本文阐述不同表型的肝巨噬细胞在肝纤维化发生发展过程中的作用，以期为纤维化的防治研究提供新思路。
- 肝纤维化 /
- 巨噬细胞 /
- 细胞极化
Abstract: Liver fibrosis is the healing reaction of chronic liver injury caused by various factors such as viral infection， alcohol， and chemical substances and is a key link in the progression of chronic liver diseases to liver cirrhosis and liver cancer. Liver macrophages are considered important mediators of liver injury and repair， and the polarization trend of macrophages has a bidirectional regulatory effect on liver fibrosis. This article reviews the role of different phenotypes of liver macrophages in the development and progression of liver fibrosis， in order to provide new ideas for the prevention and treatment of fibrosis.
- Liver Fibrosis /
- Macrophages /
- Cell Polarization

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图 1 巨噬细胞极化在肝纤维化中的调控作用机制

Figure 1. The regulatory mechanism of macrophage polarization in liver fibrosis

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参考文献(39)

[1]	KOYAMA Y, BRENNER DA. Liver inflammation and fibrosis[J]. J Clin Invest, 2017, 127( 1): 55- 64. DOI: 10.1172/JCI88881.
[2]	LIU M, HU Y, YUAN Y, et al. γδT cells suppress liver fibrosis via strong cytolysis and enhanced NK cell-mediated cytotoxicity against hepatic stellate cells[J]. Front Immunol, 2019, 10: 477. DOI: 10.3389/fimmu.2019.00477.
[3]	KRENKEL O, TACKE F. Liver macrophages in tissue homeostasis and disease[J]. Nat Rev Immunol, 2017, 17( 5): 306- 321. DOI: 10.1038/nri.2017.11.
[4]	SICA A, MANTOVANI A. Macrophage plasticity and polarization: in vivo veritas[J]. J Clin Invest, 2012, 122( 3): 787- 795. DOI: 10.1172/JCI59643.
[5]	SHAPOURI-MOGHADDAM A, MOHAMMADIAN S, VAZINI H, et al. Macrophage plasticity, polarization, and function in health and disease[J]. J Cell Physiol, 2018, 233( 9): 6425- 6440. DOI: 10.1002/jcp.26429.
[6]	WANG L, ZHANG H, SUN L, et al. Manipulation of macrophage polarization by peptide-coated gold nanoparticles and its protective effects on acute lung injury[J]. J Nanobiotechnology, 2020, 18( 1): 38. DOI: 10.1186/s12951-020-00593-7.
[7]	XU F, GUO M, HUANG W, et al. Annexin A5 regulates hepatic macrophage polarization via directly targeting PKM2 and ameliorates NASH[J]. Redox Biol, 2020, 36: 101634. DOI: 10.1016/j.redox.2020.101634.
[8]	ZHAO S, MI Y, GUAN B, et al. Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer[J]. J Hematol Oncol, 2020, 13( 1): 156. DOI: 10.1186/s13045-020-00991-2.
[9]	MA PF, GAO CC, YI J, et al. Cytotherapy with M1-polarized macrophages ameliorates liver fibrosis by modulating immune microenvironment in mice[J]. J Hepatol, 2017, 67( 4): 770- 779. DOI: 10.1016/j.jhep.2017.05.022.
[10]	YANG Y, YE YC, CHEN Y, et al. Crosstalk between hepatic tumor cells and macrophages via Wnt/β-catenin signaling promotes M2-like macrophage polarization and reinforces tumor malignant behaviors[J]. Cell Death Dis, 2018, 9( 8): 793. DOI: 10.1038/s41419-018-0818-0.
[11]	KAZANKOV K, JØRGENSEN S, THOMSEN KL, et al. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Nat Rev Gastroenterol Hepatol, 2019, 16( 3): 145- 159. DOI: 10.1038/s41575-018-0082-x.
[12]	van der HEIDE D, WEISKIRCHEN R, BANSAL R. Therapeutic targeting of hepatic macrophages for the treatment of liver diseases[J]. Front Immunol, 2019, 10: 2852. DOI: 10.3389/fimmu.2019.02852.
[13]	KRENKEL O, TACKE F. Liver macrophages in tissue homeostasis and disease[J]. Nat Rev Immunol, 2017, 17( 5): 306- 321. DOI: 10.1038/nri.2017.11.
[14]	MATSUDA M, SEKI E. Hepatic stellate cell-macrophage crosstalk in liver fibrosis and carcinogenesis[J]. Semin Liver Dis, 2020, 40( 3): 307- 320. DOI: 10.1055/s-0040-1708876.
[15]	SINGLA RD, WANG J, SINGLA DK. Regulation of Notch 1 signaling in THP-1 cells enhances M2 macrophage differentiation[J]. Am J Physiol Heart Circ Physiol, 2014, 307( 11): H1634- H1642. DOI: 10.1152/ajpheart.00896.2013.
[16]	WEI W, LI ZP, BIAN ZX, et al. Astragalus polysaccharide RAP induces macrophage phenotype polarization to M1 via the Notch signaling pathway[J]. Molecules, 2019, 24( 10): 2016. DOI: 10.3390/molecules24102016.
[17]	ZHENG S, ZHANG P, CHEN Y, et al. Inhibition of Notch signaling attenuates schistosomiasis hepatic fibrosis via blocking macrophage M2 polarization[J]. PLoS One, 2016, 11( 11): e0166808. DOI: 10.1371/journal.pone.0166808.
[18]	TRAVIS MA, SHEPPARD D. TGF-β activation and function in immunity[J]. Annu Rev Immunol, 2014, 32: 51- 82. DOI: 10.1146/annurev-immunol-032713-120257.
[19]	LU H, WU L, LIU L, et al. Quercetin ameliorates kidney injury and fibrosis by modulating M1/M2 macrophage polarization[J]. Biochem Pharmacol, 2018, 154: 203- 212. DOI: 10.1016/j.bcp.2018.05.007.
[20]	CHEN B, HUANG S, SU Y, et al. Macrophage Smad3 protects the infarcted heart, stimulating phagocytosis and regulating inflammation[J]. Circ Res, 2019, 125( 1): 55- 70. DOI: 10.1161/CIRCRESAHA.119.315069.
[21]	XIN P, XU X, DENG C, et al. The role of JAK/STAT signaling pathway and its inhibitors in diseases[J]. Int Immunopharmacol, 2020, 80: 106210. DOI: 10.1016/j.intimp.2020.106210.
[22]	WANG F, ZHANG S, JEON R, et al. Interferon gamma induces reversible metabolic reprogramming of M1 macrophages to sustain cell viability and pro-inflammatory activity[J]. EBioMedicine, 2018, 30: 303- 316. DOI: 10.1016/j.ebiom.2018.02.009.
[23]	HU X, CHEN J, WANG L, et al. Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways in macrophage activation[J]. J Leukoc Biol, 2007, 82( 2): 237- 243. DOI: 10.1189/jlb.1206763.
[24]	HE Y, GAO Y, ZHANG Q, et al. IL-4 switches microglia/macrophage M1/M2 polarization and alleviates neurological damage by modulating the JAK1/STAT6 pathway following ICH[J]. Neuroscience, 2020, 437: 161- 171. DOI: 10.1016/j.neuroscience.2020.03.008.
[25]	GAO S, ZHOU J, LIU N, et al. Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13[J]. J Mol Cell Cardiol, 2015, 85: 131- 139. DOI: 10.1016/j.yjmcc.2015.04.025.
[26]	QUERO L, TIADEN AN, HANSER E, et al. miR-221-3p drives the shift of M2-macrophages to a pro-inflammatory function by suppressing JAK3/STAT3 activation[J]. Front Immunol, 2019, 10: 3087. DOI: 10.3389/fimmu.2019.03087.
[27]	QIAN M, WANG S, GUO X, et al. Hypoxic glioma-derived exosomes deliver microRNA-1246 to induce M2 macrophage polarization by targeting TERF2IP via the STAT3 and NF-‍κB pathways[J]. Oncogene, 2020, 39( 2): 428- 442. DOI: 10.1038/s41388-019-0996-y.
[28]	BAO L, LI X. MicroRNA-32 targeting PTEN enhances M2 macrophage polarization in the glioma microenvironment and further promotes the progression of glioma[J]. Mol Cell Biochem, 2019, 460( 1-2): 67- 79. DOI: 10.1007/s11010-019-03571-2.
[29]	HU J, HUANG CX, RAO PP, et al. Inhibition of microRNA-155 attenuates sympathetic neural remodeling following myocardial infarction via reducing M1 macrophage polarization and inflammatory responses in mice[J]. Eur J Pharmacol, 2019, 851: 122- 132. DOI: 10.1016/j.ejphar.2019.02.001.
[30]	DHAR D, BAGLIERI J, KISSELEVA T, et al. Mechanisms of liver fibrosis and its role in liver cancer[J]. Exp Biol Med(Maywood), 2020, 245( 2): 96- 108. DOI: 10.1177/1535370219898141.
[31]	PRADERE JP, KLUWE J, de MINICIS S, et al. Hepatic macrophages but not dendritic cells contribute to liver fibrosis by promoting the survival of activated hepatic stellate cells in mice[J]. Hepatology, 2013, 58( 4): 1461- 1473. DOI: 10.1002/hep.26429.
[32]	KISSELEVA T, BRENNER D. Molecular and cellular mechanisms of liver fibrosis and its regression[J]. Nat Rev Gastroenterol Hepatol, 2021, 18( 3): 151- 166. DOI: 10.1038/s41575-020-00372-7.
[33]	BANSAL R, van BAARLEN J, STORM G, et al. The interplay of the Notch signaling in hepatic stellate cells and macrophages determines the fate of liver fibrogenesis[J]. Sci Rep, 2015, 5: 18272. DOI: 10.1038/srep18272.
[34]	WATANABE Y, TSUCHIYA A, SEINO S, et al. Mesenchymal stem cells and induced bone marrow-derived macrophages synergistically improve liver fibrosis in mice[J]. Stem Cells Transl Med, 2019, 8( 3): 271- 284. DOI: 10.1002/sctm.18-0105.
[35]	LUO XY, MENG XJ, CAO DC, et al. Transplantation of bone marrow mesenchymal stromal cells attenuates liver fibrosis in mice by regulating macrophage subtypes[J]. Stem Cell Res Ther, 2019, 10( 1): 16. DOI: 10.1186/s13287-018-1122-8.
[36]	WANG M, ZHANG M, FU L, et al. Liver-targeted delivery of TSG-6 by calcium phosphate nanoparticles for the management of liver fibrosis[J]. Theranostics, 2020, 10( 1): 36- 49. DOI: 10.7150/thno.37301.
[37]	SONG WJ, LI Q, MO RYU, et al. TSG-6 released from intraperitoneally injected canine adipose tissue-derived mesenchymal stem cells ameliorate inflammatory bowel disease by inducing M2 macrophage switch in mice[J]. Stem Cell Res Ther, 2018, 9( 1): 91. DOI: 10.1186/s13287-018-0841-1.
[38]	TOSELLO-TRAMPONT AC, KRUEGER P, NARAYANAN S, et al. NKp46(+) natural killer cells attenuate metabolism-induced hepatic fibrosis by regulating macrophage activation in mice[J]. Hepatology, 2016, 63( 3): 799- 812. DOI: 10.1002/hep.28389.
[39]	YUNNA C, MENGRU H, LEI W, et al. Macrophage M1/M2 polarization[J]. Eur J Pharmacol, 2020, 877: 173090. DOI: 10.1016/j.ejphar.2020.173090.