外泌体对血吸虫病肝纤维化病理进程的调节作用研究进展
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摘要
外泌体(Exosome)是一类由多种细胞形成和释放的多囊泡体,或由细胞膜产生的细胞外膜性小泡,是细胞间通信、信号传导和基因调控等信息传递的重要介质,参与几乎所有的病理、生理过程。外泌体含有细胞特异性蛋白、mRNA及miRNAs等成分。血吸虫病肝纤维化是血吸虫病发生发展过程中肝组织的病理学改变,受损的肝细胞通过释放外泌体而触发炎症,激活肝星状细胞等启动修复和(或)再生反应。外泌体参与了血吸虫病肝纤维化的形成,可能成为血吸虫病肝纤维化的新的诊断标志物,以及减轻肝纤维化病理进程的新靶点。本文就近年来有关外泌体对血吸虫病肝纤维化调节作用的研究进行综述,旨在为进一步研究和发现血吸虫病肝纤维化的药物治疗新靶点提供新思路。
Exosomes are a group of membraneous vesicles generated and released by multivesicular bodies or cell membranes in a variety of cell types. Acting as important messages between cells, they participate in almost every physiological and pathological process of living organisms. Exosomes contain specific proteins, mRNA, miRNAs, etc. and mediate intercellular communications, signal transdutions and gene expressions effectively. Exosomes are involved in the formation of hepatic fibrosis, which is the typical liver pathological change in the progression of schistosomiasis and is caused by the liver repair and(or)regeneration involving inflammation stimulated by exosomes, activated hepatic stellate cells and other related pathways in reaction to the parasite infection. Exosomes could serve as new markers for schistosomiasis hepatic fibrosis diagnosis and potential targets for its treatment. This paper briefly reviews the latest development of studies on the regulatory roles of exosomes in schistosomiasis hepatic fibrosis, so as to provide ideas for searching new treatment targets of the disease.
Exosomes are a group of membraneous vesicles generated and released by multivesicular bodies or cell membranes in a variety of cell types. Acting as important messages between cells, they participate in almost every physiological and pathological process of living organisms. Exosomes contain specific proteins, mRNA, miRNAs, etc. and mediate intercellular communications, signal transdutions and gene expressions effectively. Exosomes are involved in the formation of hepatic fibrosis, which is the typical liver pathological change in the progression of schistosomiasis and is caused by the liver repair and(or)regeneration involving inflammation stimulated by exosomes, activated hepatic stellate cells and other related pathways in reaction to the parasite infection. Exosomes could serve as new markers for schistosomiasis hepatic fibrosis diagnosis and potential targets for its treatment. This paper briefly reviews the latest development of studies on the regulatory roles of exosomes in schistosomiasis hepatic fibrosis, so as to provide ideas for searching new treatment targets of the disease.
引文
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[2]周永华,杨莹莹,范小琳,等.Th17/Treg免疫失衡在血吸虫病肝纤维化中的作用[J].中国寄生虫学与寄生虫病杂志,2017,35(1):89-92.
[3]Colley DG,Secor WE.Immunology of human schistosomiasis[J].Parasite Immunol,2014,36(8):347-357.
[4]Umezu T,Ohyashiki K,Kuroda M,et al.Leukemia cell to endothelial cell communication via exosomal miRNAs[J].Oncogene,2013,32(22):2747-2755.
[5]Tadokoro H,Umezu T,Ohyashiki K,et al.Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells[J].J Biol Chem,2013,288(48):34343-34351.
[6]郭德滨,朱向靖,潘兴华.外泌体--临床应用的潜在靶点[J].自然科学,2017,5(1):24-30.
[7]Wang J,Yeung BZ,Cui M,et al.Exosome is a mechanism of intercellular drug transfer:Application of quantitative pharmacology[J].J Control Release,2017,268:147-158.
[8]Hirsova P,Ibrahim SH,Verma VK,et al.Extracellular vesicles in liver pathobiology:Small particles with big impact[J].Hepatology,2016,64(6):2219-2233.
[9]Maji S,Matsuda A,Yan IK,et al.Extracellular vesicles in liver diseases[J].Am J Physiol Gastrointest Liver Physiol,2017,312(3):G194-G200.
[10]Szabo G,Momen-Heravi F.Extracellular vesicles in liver disease and potential as biomarkers and therapeutic targets[J].Nat Rev Gastroenterol Hepatol,2017,14(8):455-466.
[11]Lou G,Chen Z,Zheng M,et al.Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases[J].Exp Mol Med,2017,49(6):e346.
[12]Sahoo S,Losordo DW.Exosomes and cardiac repair after myocardial infarction[J].Circ Res,2014,114(2):333-344.
[13]Yang Y,Li Y,Chen X,et al.Exosomal transfer of miR-30a between cardiomyocytes regulates autophagy after hypoxia[J].J Mol Med(Berl),2016,94(6):711-724.
[14]Fujita Y,Araya J,Ito S,et al.Suppression of autophagy by extracellular vesicles promotes myofibroblast differentiation in COPDpathogenesis[J].J Extracell Vesicles,2015,4(1):28388.
[15]Robbins PD,Morelli AE.Regulation of immune responses by extracellular vesicles[J].Nat Rev Immunol,2014,14(3):195-208.
[16]Chuah C,Jones MK,Burke ML,et al.Cellular and chemokine-mediated regulation in schistosome-induced hepatic pathology[J].Trends Parasitol,2014,30(3):141-150.
[17]赵雷,杨东亮.血吸虫病肝纤维化发病机制研究[J].临床肝胆病杂志,2015,31(3):342-344.
[18]Vlassov AV,Magdaleno S,Setterquist R,et al.Exosomes:current knowledge of their composition,biological functions,and diagnostic and therapeutic potentials[J].Biochim Biophys Acta,2012,1820(7):940-948.
[19]Pan BT,Johnstone RM.Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro:selective externalization of the receptor[J].Cell,1983,33(3):967-978.
[20]Johnstone RM,Adam M,Hammond JR,et al.Vesicle formation during reticulocyte maturation.Association of plasma membrane activities with released vesicles(exosomes)[J].J Biol Chem,1987,262(19):9412-9420.
[21]李勇敏,谭小宁,马荣丽,等.中医脏腑相关理论新释--外泌体与脏腑相关理论之联系探微[J].湖南中医杂志,2017,33(2):1-4.
[22]Regev-Rudzki N,Wilson DW,Carvalho TG,et al.Cell-cell communication between malaria-infected red blood cells via exosome-like vesicles[J].Cell,2013,153(5):1120-1133.
[23]Bang C,Thum T.Exosomes:new players in cell-cell communication[J].Int J Biochem Cell Biol,2012,44(11):2060-2064.
[24]De Toro J,Herschlik L,Waldner C,et al.Emerging roles of exosomes in normal and pathological conditions:new insights for diagnosis and therapeutic applications[J].Front Immunol,2015,6:203.
[25]Witwer KW,Buzás EI,Bemis LT,et al.Standardization of sample collection,isolation and analysis methods in extracellular vesicle research[J].J Extracell Vesicles,2013,2(1):20360.
[26]Hosseini HM,Fooladi AA,Nourani MR,et al.The role of exosomes in infectious diseases[J].Inflamm Allergy Drug Targets,2013,12(1):29-37.
[27]D?ugońska H,Gatkowska J.Exosomes in the context of Toxoplasma gondii-host communication[J].Ann Parasitol,2016,62(3):169-174.
[28]Schorey JS,Harding CV.Extracellular vesicles and infectious diseases:new complexity to an old story[J].J Clin Invest,2016,126(4):1181-1189.
[29]Schorey JS,Cheng Y,Singh PP,et al.Exosomes and other extracellular vesicles in host-pathogen interactions[J].EMBO Rep,2015,16(1):24-43.
[30]Robbins PD,Dorronsoro A,Booker CN.Regulation of chronic inflammatory and immune processes by extracellular vesicles[J].JClin Invest,2016,126(4):1173-1180.
[31]Coackley G MR,Other EV.The new communicators in parasitie infection[J].Trends Parasitol,2015,31(10):477-489.
[32]Szempruch AJ,Sykes SE,Kieft R,et al.Extracellular vesicles from Trypanosoma brucei mediate virulence factor transfer and cause host anemia[J].Cell,2016,164(1/2):246-257.
[33]蔡文,张淑玲,赵雷.血吸虫病肝纤维化发病机制及相关药物作用靶点的研究进展[J].国际医学寄生虫病杂志,2012,39(4):241-245.
[34]Driguez P,McManus DP,Gobert GN.Clinical implications of recent findings in schistosome proteomics[J].Expert Rev Proteomics,2016,13(1):19-33.
[35]Hoy AM,Lundie RJ,Ivens A,et al.Parasite-derived microRNAs in host serum as novel biomarkers of helminth infection[J].PLoSNegl Trop Dis,2014,8(2):e2701.
[36]Cai P,Gobert GN,You H,et al.Circulating miRNAs:potential novel biomarkers for hepatopathology progression and diagnosis of schistosomiasis japonica in two murine models[J].PLoS Negl Trop Dis,2015,9(7):e0003965.
[37]Sotillo J,Doolan D,Loukas A.Recent advances in proteomic applications for schistosomiasis research:potential clinical impact[J].Expert Rev Proteomics,2017,14(2):171-183.
[38]He X,Tang R,Sun Y,et al.MicroR-146 blocks the activation of M1 macrophage by targeting signal transducer and activator of transcription 1 in hepatic schistosomiasis[J].EBioMedicine,2016,13:339-347.
[39]蔡卫民.认识肝纤维化与晚期血吸虫病的过去与未来[J].中国血吸虫病防治杂志,2008,20(3):235-238.
[40]Deolindo P,Evans-Osses I,Ramirez MI.Microvesicles and exosomes as vehicles between protozoan and host cell communication[J].Biochem Soc Trans,2013,41(1):252-257.
[41]王铖芸,张凡,侯敏,等.MicroRNA在小鼠血吸虫病及吡喹酮治疗中的表达特征[J].中国血吸虫病防治杂志,2014,26(2):165-168,174.
[42]Cai P,Piao X,Liu S,et al.MicroRNA-gene expression network in murine liver during Schistosoma japonicum infection[J].PLoSOne,2013,8(6):e67037.
[43]Han H,Peng J,Hong Y,et al.Comparison of the differential expression miRNAs in Wistar rats before and 10 days after S.japonicum infection[J].Parasit Vectors,2013,6:120.
[44]Johnnidis JB,Harris MH,Wheeler RT,et al.Regulation of progenitor cell proliferation and granulocyte function by microRNA-223[J].Nature,2008,451(7182):1125-1129.
[45]He X,Sai X,Chen C,et al.Host serum miR-223 is a potential new biomarker for Schistosoma japonicum infection and the response to chemotherapy[J].Parasit Vectors,2013,6:272.
[46]王欢,卢雅静,高彦茹,等.日本血吸虫可溶性虫卵抗原诱导肝纤维化相关miRNA的变化[J].中国血吸虫病防治杂志,2017,29(2):192-196.
[47]赛雪.上调宿主microRNA-203对血吸虫病肝纤维化的影响[D].上海:第二军医大学,2013.
[48]Cheng G,Luo R,Hu C,et al.Deep sequencing-based identification of pathogen-specific microRNAs in the plasma of rabbits infected with Schistosoma japonicum[J].Parasitology,2013,140(14):1751-1761.
[49]Cai P,Piao X,Hao L,et al.A deep analysis of the small non-coding RNA population in Schistosoma japonicum eggs[J].PLoS One,2013,8(5):e64003.
[50]陈超,白瑞璞,何兴,等.吡喹酮对日本血吸虫病肝纤维化的治疗作用及宿主mi RNA表达变化[J].国际医学寄生虫病杂志,2015,42(1):1-5,13.
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