巨噬细胞表型转换在肝纤维化进展及逆转中的作用

摘要/Abstract

摘要： 慢性肝病的进程常涉及慢性实质损伤、炎症反应的持续激活以及纤维生成和伤口愈合反应的持续激活。其中,巨噬细胞是肝脏的关键细胞,对于响应肝损伤引起的炎症反应和维持组织稳态至关重要。目前普遍认为巨噬细胞在肝纤维化进展和逆转过程中具有异质性,其可以根据组织微环境的不同而发生表型转换。巨噬细胞不仅在肝纤维化进展中起到促进作用,其还可以在逆转阶段通过分泌基质金属蛋白酶,促进胶原纤维水解,促进肝纤维化逆转。本文就巨噬细胞表型转换在肝纤维化进展及逆转中的作用作一综述。

王晓凡, 丛敏, 贾继东. 巨噬细胞表型转换在肝纤维化进展及逆转中的作用[J]. 肝脏, 2023, 28(11): 1264-1268.

参考文献

[1] Diseases GBD, Injuries C. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019[J]. Lancet,2020,396:1204-1222.
[2] Asrani SK, Devarbhavi H, Eaton J, et al. Burden of liver diseases in the world[J]. J Hepatol,2019,70:151-171.
[3] Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression[J]. Nat Rev Gastroenterol Hepatol,2021,18:151-166.
[4] Higashi T, Friedman SL, Hoshida Y. Hepatic stellate cells as key target in liver fibrosis[J]. Adv Drug Deliv Rev,2017,121:27-42.
[5] Cheng D, Chai J, Wang H, et al. Hepatic macrophages: Key players in the development and progression of liver fibrosis[J]. Liver Int,2021,41:2279-2294.
[6] Guillot A, Tacke F. Liver Macrophages: Old Dogmas and New Insights[J]. Hepatol Commun,2019,3:730-743.
[7] Guilliams M, Scott CL. Liver macrophages in health and disease[J]. Immunity,2022,55:1515-1529.
[8] Krenkel O, Tacke F. Liver macrophages in tissue homeostasis and disease[J]. Nat Rev Immunol,2017,17:306-321.
[9] Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease[J]. Nature,2013,496:445-455.
[10] Gomez Perdiguero E, Klapproth K, Schulz C, et al. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors[J]. Nature,2015,518:547-551.
[11] Roohani S, Tacke F. Liver Injury and the Macrophage Issue: Molecular and Mechanistic Facts and Their Clinical Relevance[J]. Int J Mol Sci,2021,22.
[12] Scott CL, Zheng F, De Baetselier P, et al. Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells[J]. Nat Commun,2016,7:10321.
[13] Kinoshita M, Uchida T, Sato A, et al. Characterization of two F4/80-positive Kupffer cell subsets by their function and phenotype in mice[J]. J Hepatol,2010,53:903-910.
[14] Heymann F, Peusquens J, Ludwig-Portugall I, et al. Liver inflammation abrogates immunological tolerance induced by Kupffer cells[J]. Hepatology,2015,62:279-291.
[15] Shi C, Pamer EG. Monocyte recruitment during infection and inflammation[J]. Nat Rev Immunol,2011,11:762-774.
[16] Tacke F, Zimmermann HW. Macrophage heterogeneity in liver injury and fibrosis[J]. J Hepatol,2014,60:1090-1096.
[17] Liaskou E, Zimmermann HW, Li KK, et al. Monocyte subsets in human liver disease show distinct phenotypic and functional characteristics[J]. Hepatology,2013,57:385-398.
[18] Ozanska A, Szymczak D, Rybka J. Pattern of human monocyte subpopulations in health and disease[J]. Scand J Immunol,2020,92:e12883.
[19] Atri C, Guerfali FZ, Laouini D. Role of Human Macrophage Polarization in Inflammation during Infectious Diseases[J]. Int J Mol Sci,2018,19.
[20] Munoz J, Akhavan NS, Mullins AP, et al. Macrophage Polarization and Osteoporosis: A Review[J]. Nutrients,2020,12.
[21] Yao Y, Xu XH, Jin L. Macrophage Polarization in Physiological and Pathological Pregnancy[J]. Front Immunol,2019,10:792.
[22] Sica A, Erreni M, Allavena P, et al. Macrophage polarization in pathology[J]. Cell Mol Life Sci,2015,72:4111-4126.
[23] 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.
[24] Wu X, Wang Z, Shi J, et al. Macrophage polarization toward M1 phenotype through NF-kappaB signaling in patients with Behcet’s disease[J]. Arthritis Res Ther,2022,24:249.
[25] Chen W, Liu Y, Chen J, et al. The Notch signaling pathway regulates macrophage polarization in liver diseases[J]. Int Immunopharmacol,2021,99:107938.
[26] Hu N, Zhang X, Zhang X, et al. Inhibition of Notch activity suppresses hyperglycemia-augmented polarization of macrophages to the M1 phenotype and alleviates acute pancreatitis[J]. Clinical Science,2022,136:455-471.
[27] Ma T, Li X, Zhu Y, et al. Excessive Activation of Notch Signaling in Macrophages Promote Kidney Inflammation, Fibrosis, and Necroptosis[J]. Front Immunol,2022,13:835879.
[28] Deng S, Jin P, Liu S, et al. Recruitment of regulatory T cells with rCCL17 promotes M2 microglia/macrophage polarization through TGFβ/TGFβR/Smad2/3 pathway in a mouse model of intracerebral hemorrhage[J]. Experimental Neurology,2023,367.
[29] Liu F, Qiu H, Xue M, et al. MSC-secreted TGF-beta regulates lipopolysaccharide-stimulated macrophage M2-like polarization via the Akt/FoxO1 pathway[J]. Stem Cell Res Ther,2019,10:345.
[30] Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance[J]. Nature,2007,447:1116-1120.
[31] Qiao N, Lin Y, Wang Z, et al. Maresin1 Promotes M2 Macrophage Polarization Through Peroxisome Proliferator-Activated Receptor-gamma Activation to Expedite Resolution of Acute Lung Injury[J]. J Surg Res,2020,256:584-594.
[32] Vergadi E, Ieronymaki E, Lyroni K, et al. Akt Signaling Pathway in Macrophage Activation and M1/M2 Polarization[J]. J Immunol,2017,198:1006-1014.
[33] Yu T, Gao M, Yang P, et al. Insulin promotes macrophage phenotype transition through PI3K/Akt and PPAR-gamma signaling during diabetic wound healing[J]. J Cell Physiol,2019,234:4217-4231.
[34] Le F, Yang L, Han Y, et al. TPL Inhibits the Invasion and Migration of Drug-Resistant Ovarian Cancer by Targeting the PI3K/AKT/NF-kappaB-Signaling Pathway to Inhibit the Polarization of M2 TAMs[J]. Front Oncol,2021,11:704001.
[35] Huangfu N, Zheng W, Xu Z, et al. RBM4 regulates M1 macrophages polarization through targeting STAT1-mediated glycolysis[J]. Int Immunopharmacol,2020,83:106432.
[36] 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.
[37] Lu TX, Rothenberg ME. MicroRNA[J]. J Allergy Clin Immunol,2018,141:1202-1207.
[38] Guo Q, Zhu X, Wei R, et al. miR-130b-3p regulates M1 macrophage polarization via targeting IRF1[J]. J Cell Physiol,2021,236:2008-2022.
[39] Zhang Y, Le X, Zheng S, et al. MicroRNA-146a-5p-modified human umbilical cord mesenchymal stem cells enhance protection against diabetic nephropathy in rats through facilitating M2 macrophage polarization[J]. Stem Cell Res Ther,2022,13:171.
[40] Tan Z, Sun H, Xue T, et al. Liver Fibrosis: Therapeutic Targets and Advances in Drug Therapy[J]. Front Cell Dev Biol,2021,9:730176.
[41] Wen Y, Lambrecht J, Ju C, et al. Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities[J]. Cell Mol Immunol,2021,18:45-56.
[42] Matsuda M, Seki E. Hepatic Stellate Cell-Macrophage Crosstalk in Liver Fibrosis and Carcinogenesis[J]. Semin Liver Dis,2020,40:307-320.
[43] 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,2013,58:1461-1473.
[44] Imamura M, Ogawa T, Sasaguri Y, et al. Suppression of macrophage infiltration inhibits activation of hepatic stellate cells and liver fibrogenesis in rats[J]. Gastroenterology,2005,128:138-146.
[45] Rao J, Wang H, Ni M, et al. FSTL1 promotes liver fibrosis by reprogramming macrophage function through modulating the intracellular function of PKM2[J]. Gut,2022,71:2539-2550.
[46] Xu L, Chen Y, Nagashimada M, et al. CC chemokine ligand 3 deficiency ameliorates diet-induced steatohepatitis by regulating liver macrophage recruitment and M1/M2 status in mice[J]. Metabolism,2021,125:154914.
[47] Fang W, Deng Z, Benadjaoud F, et al. Cathepsin B deficiency ameliorates liver lipid deposition, inflammatory cell infiltration, and fibrosis after diet-induced nonalcoholic steatohepatitis[J]. Transl Res,2020,222:28-40.
[48] Cao Y, Mai W, Li R, et al. Macrophages evoke autophagy of hepatic stellate cells to promote liver fibrosis in NAFLD mice via the PGE2/EP4 pathway[J]. Cell Mol Life Sci,2022,79:303.
[49] Xue J, Xiao T, Wei S, et al. miR-21-regulated M2 polarization of macrophage is involved in arsenicosis-induced hepatic fibrosis through the activation of hepatic stellate cells[J]. J Cell Physiol,2021,236:6025-6041.
[50] Bility MT, Nio K, Li F, et al. Chronic hepatitis C infection-induced liver fibrogenesis is associated with M2 macrophage activation[J]. Sci Rep,2016,6:39520.
[51] Karlmark KR, Weiskirchen R, Zimmermann HW, et al. Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis[J]. Hepatology,2009,50:261-274.
[52] Baeck C, Wei X, Bartneck M, et al. Pharmacological inhibition of the chemokine C-C motif chemokine ligand 2 (monocyte chemoattractant protein 1) accelerates liver fibrosis regression by suppressing Ly-6C(+) macrophage infiltration in mice[J]. Hepatology,2014,59:1060-1072.
[53] Chang ML, Lin YT, Kung HN, et al. A triterpenoid-enriched extract of bitter melon leaves alleviates hepatic fibrosis by inhibiting inflammatory responses in carbon tetrachloride-treated mice[J]. Food Funct,2021,12:7805-7815.
[54] Campana L, Iredale JP. Regression of Liver Fibrosis[J]. Semin Liver Dis,2017,37:1-10.
[55] Ramachandran P, Pellicoro A, Vernon MA, et al. Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis[J]. Proc Natl Acad Sci U S A,2012,109:E3186-3195.
[56] 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,2017,67:770-779.
[57] Li YH, Shen S, Shao T, et al. Mesenchymal stem cells attenuate liver fibrosis by targeting Ly6C(hi/lo) macrophages through activating the cytokine-paracrine and apoptotic pathways[J]. Cell Death Discov,2021,7:239.
[58] Zheng Z, Wang H, Li L, et al. Splenectomy enhances the Ly6C(low) phenotype in hepatic macrophages by activating the ERK1/2 pathway during liver fibrosis[J]. Int Immunopharmacol,2020,86:106762.
[59] Mosser DM, Hamidzadeh K, Goncalves R. Macrophages and the maintenance of homeostasis[J]. Cell Mol Immunol,2021,18:579-587.
[60] 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.
[61] Liu C, Schönke M, Spoorenberg B, et al. FGF21 protects against hepatic lipotoxicity and macrophage activation to attenuate fibrogenesis in nonalcoholic steatohepatitis[J]. eLife,2023,12.
[62] Friedman SL, Ratziu V, Harrison SA, et al. A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis[J]. Hepatology,2018,67:1754-1767.
[63] Moroni F, Dwyer BJ, Graham C, et al. Safety profile of autologous macrophage therapy for liver cirrhosis[J]. Nat Med,2019,25:1560-1565.