Role of Wnt signal-mediated crosstalk between hepatic macrophages and hepatic progenitor cells in the development and repair of liver fibrosis
-
摘要: 肝脏巨噬细胞和肝祖细胞在肝纤维化的发生与修复中发挥着重要作用,巨噬细胞的极化状态可影响肝祖细胞的分化取向,Wnt信号通路在巨噬细胞与肝祖细胞相互作用中发挥关键"桥梁"作用。重点概述了在肝纤维化病理状态下,巨噬细胞、肝祖细胞的作用及其二者之间的"对话"机制。指出未来需要对肝巨噬细胞的基因组和表型进行深入研究,明确其调控肝祖细胞分化的机制,以期为肝纤维化的治疗提供依据。Abstract: Hepatic macrophages and hepatic progenitor cells play an important role in the development and repair of liver fibrosis. The polarized state of macrophages can affect the differentiation orientation of hepatic progenitor cells,and the Wnt signaling pathway may play a key role in the crosstalk between hepatic macrophages and hepatic progenitor cells. This article overviews the role of macrophages and hepatic progenitor cells and the mechanism of the crosstalk between them in the pathological state of liver fibrosis. It is pointed out that in-depth studies are needed to investigate the genome and phenotype of hepatic macrophages and clarify the mechanism of action of macrophages in regulating the differentiation of hepatic progenitor cells,in order to provide a basis for the treatment of liver fibrosis.
-
Key words:
- liver cirrhosis /
- macrophages /
- hepatocyte progenitor cells /
- Wnt proteins /
- signal transduction
-
[1] SANTORO R,MANGIA A. Progress in promising anti-fibrotic therapies[J]. Expert Rev Gastroenterol Hepatol,2019,13(12):1145-1152. [2] EPELMAN S,LAVINE KJ,RANDOLPH GJ. Origin and functions of tissue macrophages[J]. Immunity,2014,41(1):21-35. [3] WYNN TA,VANNELLA KM. Macrophages in tissue repair,regeneration,and fibrosis[J]. Immunity,2016,44(3):450-462. [4] HUME DA,IRVINE KM,PRIDANS C. The mononuclear phagocyte system:The relationship between monocytes and macrophages[J]. Trends Immunol,2019,40(2):98-112. [5] GOMEZ PERDIGUERO E,KLAPPROTH K,SCHULZ C,et al.Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors[J]. Nature,2015,43(9):s64. [6] GANZ T. Macrophages and systemic iron homeostasis[J]. J Innate Immun,2012,4(5-6):446453. [7] SCHULZ C,GOMEZ PERDIGUERO E,CHORRO L,et al. A lineage of myeloid cells independent of Myb and hematopoietic stem cells[J]. Science,2012,336(6077):8690. [8] DAVIES LC,JENKINS SJ,ALLEN JE,et al. Tissueresident macrophages[J]. Nat Immunol,2013,14(10):986995. [9] VAROL C,MILDNER A,JUNG S. Macrophages:Development and tissue specialization[J]. Annu Rev Immunol,2015,33:643-675. [10] HOEFFEL G,GINHOUX F. Fetal monocytes and the origins of tissue-resident macrophages[J]. Cell Immunol,2018,330:5-15. [11] MOSSANEN JC,KRENKEL O,ERGEN C,et al. Chemokine(CC motif)receptor 2-positive monocytes aggravate the early phase of acetaminophen-induced acute liver injury?[J]. Hepatology,2016,64(5):1667-1682. [12] DAL-SECCO D,WANG J,ZENG Z,et al. A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+monocytes at a site of sterile injury[J]. J Exp Med,2015,212(4):447-456. [13] PRADERE JP,KLUWE J,MINICIS SD,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. [14] TACKE F. Targeting hepatic macrophages to treat liver diseases[J]. J Hepatol,2017,66(6):1300-1312. [15] SWIRSKI FK,NAHRENDORF M,ETZRODT M,et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites[J]. Science,2009,325(5940):612-616. [16] VANNELLA KM,WYNN TA. Mechanisms of organ injury and repair by macrophages[J]. Annu Rev Physiol,2017,79:593-617. [17] MURRAY PJ,WYNN TA. Protective and pathogenic functions of macrophage subsets[J]. Nat Rev Immunol,2011,11(11):723-737. [18] SCHAUER D,STARLINGER P,ZAJC P,et al. Monocytes with angiogenic potential are selectively induced by liver resection and accumulate near the site of liver regeneration[J]. BMC Immunol,2014,15(1):50. [19] SICA A,INVERNIZZI P,MANTOVANI A. Macrophage plasticity and polarization in liver homeostasis and pathology[J].Hepatology,2014,59(5):2034-2042. [20] MURRAY PJ,ALLEN JE,BISWAS SK,et al. Macrophage activation and polarization:Nomenclature and experimental guidelines[J]. Immunity,2014,41(1):14-20. [21] ODEGAARD JI,CHAWLA A. Alternative macrophage activation and metabolism[J]. Annu Rev Pathol,2011,6:275-297. [22] JANATMAKAN F,ZADEH FJ,ALIZADEH M,et al. The comparison of the effect of mannitol and nacetyl cysteine on liver function in partial hepatectomy[J]. Anesth Pain Med,2018,8(5):e79677. [23] MEIJER C,WIEZER MJ,DIEHL AM,et al. Kupffer cell depletion by CI2MDP-liposomes alters hepatic cytokine expression and delays liver regeneration after partial hepatectomy[J].Liver,2000,20(1):66-77. [24] PARK JK,SHAO M,KIM MY,et al. An endoplasmic reticulum protein,Nogo-B,facilitates alcoholic liver disease through regulation of Kupffer cell polarization[J]. Hepatology,2017,65(5):1720-1734. [25] BARBAY V,HOUSSARI M,MEKKI M,et al. Role of M2-like macrophage recruitment during angiogenic growth factor therapy[J]. Angiogenesis,2015,18(2):191-200. [26] TAN Q,HU J,YU X,et al. The role of IL-1 family members and Kupffer cells in liver regeneration[J]. Biomed Res Int,2016,2016:6495793. [27] GONG W,HUANG F,SUN L,et al. Toll-like receptor-2regulates macrophage polarization induced by excretory-secretory antigens from Schistosoma japonicum eggs and promotes liver pathology in murine schistosomiasis[J]. PLo S Neglect Trop D,2018,12(12):e0007000. [28] SHIRABE K,MANO Y,MUTO J,et al. Role of tumor-associated macrophages in the progression of hepatocellular carcinoma[J]. Surg Today,2012,42(1):1-7. [29] LANE SW,WILLIAMS DA,WATT FM. Modulating the stem cell niche for tissue regeneration[J]. Nat Biotechnol,2014,32(8):795-803. [30] WYNN TA,CHAWLA A,POLLARD JW. Macrophage biology in development,homeostasis and disease[J]. Nature,2013,496(7446):445-455. [31] SAHA S,ARANDA E,HAYAKAWA Y,et al. Macrophagederived extracellular vesicle-packaged WNTs rescue intestinal stem cells and enhance survival after radiation injury[J].Nat Commun,2016,7:13096. [32] CHEN J,ZHANG X,XU Y,et al. Hepatic progenitor cells contribute to the progression of 2-acetylaminofluorene/carbon tetrachloride-induced cirrhosis via the non-canonical Wnt pathway[J]. PLo S One,2015,10(6):e0130310. [33] JIANG F,PARSONS CJ,STEFANOVIC B. Gene expression profile of quiescent and activated rat hepatic stellate cells implicates Wnt signaling pathway in activation[J]. J Hepatol,2006,45(3):401-409. [34] TIRNITZ-PARKER JE,VIEBAHN CS,JAKUBOWSKI A,et al.Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells[J]. Hepatology,2010,52(1):291-302. [35] LIU W,JING Y,GAO L,et al. Lipopolysaccharide induces the differentiation of hepatic progenitor cells into myofibroblasts constitutes the hepatocarcinogenesis-associated microenvironment[J]. Cell Death Differ,2020,27:85-101. [36] NOVO E,di BONZO LV,CANNITO S,et al. Hepatic myofibroblasts:A heterogeneous population of multifunctional cells in liver fibrogenesis[J]. Int J Biochem Cell Biol,2009,41(11):2089-2093. [37] KITADE M,KAJI K,NISHIMURA N,et al. Blocking development of liver fibrosis augments hepatic progenitor cell-derived liver regeneration in a mouse chronic liver injury model[J]. Hepatol Res,2019,49(9):1034-1045. [38] SAVNEET K,HAMDA S,BHAT MH. Hepatic progenitor cells in action:Liver regeneration or fibrosis?[J]. Am J Pathol,2015,185(9):2342-2350. [39] BOULTER L,GOVAERE O,BIRD T G,et al. Macrophagederived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease[J]. Nat Med,2012,18(4):572-579. [40] FENG Y,REN J,GUI Y,et al. Wnt/β-Catenin-promoted macrophage alternative activation contributes to kidney fibrosis[J]. J Am Soc Nephrol,2018,29(1):182-193. [41] CARPINO G,NOBILI V,RENZI A,et al. Macrophage activation in pediatric nonalcoholic fatty liver disease(NAFLD)correlates with hepatic progenitor cell response via Wnt3a pathway[J]. PLo S One,2016,11(6):e0157246. [42] DONG X,LIU J,XU Y,et al. Role of macrophages in experimental liver injury and repair in mice[J]. Exp Ther Med,2019,17(5):3835-3847.
本文二维码
计量
- 文章访问数: 914
- HTML全文浏览量: 42
- PDF下载量: 200
- 被引次数: 0