中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 40 Issue 9
Sep.  2024
Turn off MathJax
Article Contents

Regulatory mechanism of exosomes in liver failure and the application value in diagnosis and treatment

DOI: 10.12449/JCH240928
Research funding:

Natural Science Foundation of Hebei Province (H2023206042);

Government Funding for Excellent Clinical Medicine Talent Program (ZF2023082)

More Information
  • Corresponding author: WANG Yadong, wangyadong@hebmu.edu.cn (ORCID: 0000-0003-0140-0674)
  • Received Date: 2023-12-28
  • Accepted Date: 2024-02-08
  • Published Date: 2024-09-25
  • Exosomes are an important vehicle for mediating material transportation and information transmission between cells, and the exosomes derived from hepatocytes, liver stem cells or extrahepatic mesenchymal stem cells promote the recovery and regeneration of damaged hepatocytes by inhibiting immune inflammatory response, antagonizing against oxidative stress and apoptosis, and inducing autophagy, thereby exerting a protective effect against liver failure. This article reviews the molecular mechanism of exosomes in regulating the pathogenesis of liver failure and its effect on the development, progression, and prognosis of liver failure, in order to assess the potential value of exosomes as a diagnostic marker and a therapeutic target.

     

  • loading
  • [1]
    SHEN MY, SHEN Y, FAN XL, et al. Roles of macrophages and exosomes in liver diseases[J]. Front Med(Lausanne), 2020, 7: 583691. DOI: 10.3389/fmed.2020.583691.
    [2]
    LIU B, WANG JC, WANG GC, et al. Hepatocyte-derived exosomes deliver H2AFJ to hepatic stellate cells and promote liver fibrosis via the MAPK/STMN1 axis activation[J]. Int Immunopharmacol, 2023, 115: 109605. DOI: 10.1016/j.intimp.2022.109605.
    [3]
    DASGUPTA D, NAKAO Y, MAUER AS, et al. IRE1A stimulates hepatocyte-derived extracellular vesicles that promote inflammation in mice with steatohepatitis[J]. Gastroenterology, 2020, 159( 4): 1487- 1503. e 17. DOI: 10.1053/j.gastro.2020.06.031.
    [4]
    SHABANGU CS, HUANG JF, HSIAO HH, et al. Liquid biopsy for the diagnosis of viral hepatitis, fatty liver steatosis, and alcoholic liver diseases[J]. Int J Mol Sci, 2020, 21( 10): 3732. DOI: 10.3390/ijms21103732.
    [5]
    LIU XL, PAN Q, CAO HX, et al. Lipotoxic hepatocyte-derived exosomal microRNA 192-5p activates macrophages through rictor/akt/forkhead box transcription factor O1 signaling in nonalcoholic fatty liver disease[J]. Hepatology, 2020, 72( 2): 454- 469. DOI: 10.1002/hep.31050.
    [6]
    PAN Y, TAN WF, YANG MQ, et al. The therapeutic potential of exosomes derived from different cell sources in liver diseases[J]. Am J Physiol Gastrointest Liver Physiol, 2022, 322( 4): G397- G404. DOI: 10.1152/ajpgi.00054.2021.
    [7]
    JIAO Y, LU W, XU P, et al. Hepatocyte-derived exosome may be as a biomarker of liver regeneration and prognostic valuation in patients with acute-on-chronic liver failure[J]. Hepatol Int, 2021, 15( 4): 957- 969. DOI: 10.1007/s12072-021-10217-3.
    [8]
    MASTORIDIS S, PATEL V, CHRISTAKOUDI S, et al. Impact of liver failure on the circulating extracellular vesicle miRNA repertoire[J]. Hepatol Res, 2023, 53( 8): 771- 785. DOI: 10.1111/hepr.13909.
    [9]
    DING Y, LUO QL, QUE HY, et al. Mesenchymal stem cell-derived exosomes: A promising therapeutic agent for the treatment of liver diseases[J]. Int J Mol Sci, 2022, 23( 18): 10972. DOI: 10.3390/ijms231810972.
    [10]
    LU XF, GUO HJ, WEI XY, et al. Current status and prospect of delivery vehicle based on mesenchymal stem cell-derived exosomes in liver diseases[J]. Int J Nanomedicine, 2023, 18: 2873- 2890. DOI: 10.2147/IJN.S404925.
    [11]
    ELSHARKASY OM, NORDIN JZ, HAGEY DW, et al. Extracellular vesicles as drug delivery systems: Why and how?[J]. Adv Drug Deliv Rev, 2020, 159: 332- 343. DOI: 10.1016/j.addr.2020.04.004.
    [12]
    ZHANG SQ, HOU Y, YANG J, et al. Application of mesenchymal stem cell exosomes and their drug-loading systems in acute liver failure[J]. J Cell Mol Med, 2020, 24( 13): 7082- 7093. DOI: 10.1111/jcmm.15290.
    [13]
    ZHANG SQ, JIANG LR, HU HZ, et al. Pretreatment of exosomes derived from hUCMSCs with TNF-α ameliorates acute liver failure by inhibiting the activation of NLRP3 in macrophage[J]. Life Sci, 2020, 246: 117401. DOI: 10.1016/j.lfs.2020.117401.
    [14]
    DENG CQ, HU J, HE L, et al. Daucosterol combined with umbilical cord mesenchymal stem cell-derived exosomes can alleviate liver damage in liver failure mice by regulating the IL-6/STAT3 signaling pathway[J]. Cancer Biol Ther, 2023, 24( 1): 2184150. DOI: 10.1080/15384047.2023.2184150.
    [15]
    LIU YN, LOU GH, LI AC, et al. AMSC-derived exosomes alleviate lipopolysaccharide/d-galactosamine-induced acute liver failure by miR-17-mediated reduction of TXNIP/NLRP3 inflammasome activation in macrophages[J]. EBioMedicine, 2018, 36: 140- 150. DOI: 10.1016/j.ebiom.2018.08.054.
    [16]
    CHEN L, CHEN RJ, KEMPER S, et al. Therapeutic effects of serum extracellular vesicles in liver fibrosis[J]. J Extracell Vesicles, 2018, 7( 1): 1461505. DOI: 10.1080/20013078.2018.1461505.
    [17]
    WU HY, ZHANG XC, JIA BB, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acetaminophen-induced acute liver failure through activating ERK and IGF-1R/PI3K/AKT signaling pathway[J]. J Pharmacol Sci, 2021, 147( 1): 143- 155. DOI: 10.1016/j.jphs.2021.06.008.
    [18]
    YAN YM, JIANG WQ, TAN YW, et al. hucMSC exosome-derived GPX1 is required for the recovery of hepatic oxidant injury[J]. Mol Ther, 2017, 25( 2): 465- 479. DOI: 10.1016/j.ymthe.2016.11.019.
    [19]
    ZHAO SX, LIU Y, PU ZH. Bone marrow mesenchymal stem cell-derived exosomes attenuate D-GaIN/LPS-induced hepatocyte apoptosis by activating autophagy in vitro[J]. Drug Des Devel Ther, 2019, 13: 2887- 2897. DOI: 10.2147/DDDT.S220190.
    [20]
    LIN DN, CHEN H, XIONG J, et al. Mesenchymal stem cells exosomal let-7a-5p improve autophagic flux and alleviate liver injury in acute-on-chronic liver failure by promoting nuclear expression of TFEB[J]. Cell Death Dis, 2022, 13( 10): 865. DOI: 10.1038/s41419-022-05303-9.
    [21]
    YANG B, DUAN W, WEI L, et al. Bone marrow mesenchymal stem cell-derived hepatocyte-like cell exosomes reduce hepatic ischemia/reperfusion injury by enhancing autophagy[J]. Stem Cells Dev, 2020, 29( 6): 372- 379. DOI: 10.1089/scd.2019.0194.
    [22]
    ZHANG L, SONG YL, CHEN L, et al. MiR-20a-containing exosomes from umbilical cord mesenchymal stem cells alleviates liver ischemia/reperfusion injury[J]. J Cell Physiol, 2020, 235( 4): 3698- 3710. DOI: 10.1002/jcp.29264.
    [23]
    XUE TM, YAM JWP. Role of small extracellular vesicles in liver diseases: Pathogenesis, diagnosis, and treatment[J]. J Clin Transl Hepatol, 2022, 10( 6): 1176- 1185. DOI: 10.14218/JCTH.2022.00008.
    [24]
    BALA S, TILAHU Y, TAHAA O, et al. Increased microRNA-155 expression in the serum and peripheral monocytes in chronic HCV infection[J]. Transl Med, 2012, 10: 151. DOI: 10.1186/1479-5876-10-151.
    [25]
    XU WL, YU MX, WU YK, et al. Plasma-derived exosomal SncRNA as a promising diagnostic biomarker for early detection of HBV-related acute-on-chronic liver failure[J]. Front Cell Infect Microbiol, 2022, 12: 923300. DOI: 10.3389/fcimb.2022.923300.
    [26]
    CHEN JJ, XU QS, ZHANG Y, et al. RNA profiling analysis of the serum exosomes derived from patients with chronic hepatitis and acute-on-chronic liver failure caused by HBV[J]. Sci Rep, 2020, 10( 1): 1528. DOI: 10.1038/s41598-020-58233-x.
    [27]
    GAO S, FAN YC, HAN LY, et al. Serum exosomal long noncoding RNA nuclear-enriched abundant transcript 1 predicts 90-day mortality in acute-on-chronic hepatitis B liver failure[J]. Expert Rev Clin Immunol, 2021, 17( 7): 789- 797. DOI: 10.1080/1744666X.2021.1933442.
    [28]
    SUN CX, HAN LY, WANG K, et al. Serum exosomal long noncoding RNA growth arrest-specific 5 predicts 3-month mortality in acute-on-chronic hepatitis B liver failure[J]. J Inflamm Res, 2023, 16: 4603- 4616. DOI: 10.2147/JIR.S423321.
    [29]
    XIANG Z, JIANG B, LI W, et al. The diagnostic and prognostic value of serum exosome-derived carbamoyl phosphate synthase 1 in HEV-related acute liver failure patients[J]. J Med Virol, 2022, 94( 10): 5015- 5025. DOI: 10.1002/jmv.27961.
    [30]
    HARRELL CR, PAVLOVIC D, DJONOV V, et al. Therapeutic potential of mesenchymal stem cells in the treatment of acute liver failure[J]. World J Gastroenterol, 2022, 28( 28): 3627- 3636. DOI: 10.3748/wjg.v28.i28.3627.
    [31]
    SHOKRAVI S, BORISOV V, ZAMAN BA, et al. Mesenchymal stromal cells(MSCs) and their exosome in acute liver failure(ALF): A comprehensive review[J]. Stem Cell Res Ther, 2022, 13( 1): 192. DOI: 10.1186/s13287-022-02825-z.
    [32]
    SHAO MY, XU Q, WU ZR, et al. Exosomes derived from human umbilical cord mesenchymal stem cells ameliorate IL-6-induced acute liver injury through miR-455-3p[J]. Stem Cell Res Ther, 2020, 11( 1): 37. DOI: 10.1186/s13287-020-1550-0.
    [33]
    CHEN L, XIANG BY, WANG XJ, et al. Exosomes derived from human menstrual blood-derived stem cells alleviate fulminant hepatic failure[J]. Stem Cell Res Ther, 2017, 8( 1): 9. DOI: 10.1186/s13287-016-0453-6.
    [34]
    ZHANG J, GAO J, LIN DN, et al. Potential networks regulated by MSCs in acute-on-chronic liver failure: Exosomal miRNAs and intracellular target genes[J]. Front Genet, 2021, 12: 650536. DOI: 10.3389/fgene.2021.650536.
    [35]
    ZHENG L, LI Z, LING W, et al. Exosomes derived from dendritic cells attenuate liver injury by modulating the balance of Treg and Th17 cells after ischemia reperfusion[J]. Cell Physiol Biochem, 2018, 46( 2): 740- 756. DOI: 10.1159/000488733.
    [36]
    CALLERI A, ROGGIO D, NAVARRO-TABLEROS V, et al. Protective effects of human liver stem cell-derived extracellular vesicles in a mouse model of hepatic ischemia-reperfusion injury[J]. Stem Cell Rev Rep, 2021, 17( 2): 459- 470. DOI: 10.1007/s12015-020-10078-7.
    [37]
    NOJIMA H, FREEMAN CM, SCHUSTER RM, et al. Hepatocyte exosomes mediate liver repair and regeneration via sphingosine-1-phosphate[J]. J Hepatol, 2016, 64( 1): 60- 68. DOI: 10.1016/j.jhep.2015.07.030.
    [38]
    LU W, TANG HX, LI SS, et al. Extracellular vesicles as potential biomarkers and treatment options for liver failure: A systematic review up to March 2022[J]. Front Immunol, 2023, 14: 1116518. DOI: 10.3389/fimmu.2023.1116518.
    [39]
    CHEN Q, JIN MX, WANG SM, et al. Establishing an hTERT-driven immortalized umbilical cord-derived mesenchymal stem cell line and its therapeutic application in mice with liver failure[J]. J Tissue Eng, 2023, 14: 20417314231200328. DOI: 10.1177/20417314231200328.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(1)

    Article Metrics

    Article views (132) PDF downloads(18) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return