Semin Liver Dis
DOI: 10.1055/a-2494-2233
Review Article

Extracellular Vesicles and Micro-RNAs in Liver Disease

Alexander M. Washington
1   Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
2   Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota
,
Enis Kostallari
1   Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
3   Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota
› Institutsangaben
Funding This study was supported by the NIH R01 DK136511, Mayo Clinic Center for Biomedical Discoveries, Gilead Liver Scholar award (to E.K.) and Mayo Clinic Graduate School of Biomedical Sciences stipend (to A.M.W.).


Abstract

Progression of liver disease is dependent on intercellular signaling, including those mediated by extracellular vesicles (EVs). Within these EVs, microRNAs (miRNAs) are packaged to selectively silence gene expression in recipient cells for upregulating or downregulating a specific pathway. Injured hepatocytes secrete EV-associated miRNAs which can be taken up by liver sinusoidal endothelial cells, immune cells, hepatic stellate cells, and other cell types. In addition, these recipient cells will secrete their own EV-associated miRNAs to propagate a response throughout the tissue and the circulation. In this review, we comment on the implications of EV-miRNAs in the progression of alcohol-associated liver disease, metabolic dysfunction-associated steatohepatitis, viral and parasitic infections, liver fibrosis, and liver malignancies. We summarize how circulating miRNAs can be used as biomarkers and the potential of utilizing EVs and miRNAs as therapeutic methods to treat liver disease.

Author Contribution

E.K. conceived and supervised the study; A.W. and E.K. wrote and revised the manuscript.




Publikationsverlauf

Accepted Manuscript online:
03. Dezember 2024

Artikel online veröffentlicht:
24. Dezember 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Marcellin P, Kutala BK. Liver diseases: a major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int 2018; 38 (Suppl. 01) 2-6
  • 2 Paik JM, Golabi P, Younossi Y, Mishra A, Younossi ZM. Changes in the global burden of chronic liver diseases from 2012 to 2017: the growing impact of NAFLD. Hepatology 2020; 72 (05) 1605-1616
  • 3 Kostallari E, Valainathan S, Biquard L, Shah VH, Rautou PE. Role of extracellular vesicles in liver diseases and their therapeutic potential. Adv Drug Deliv Rev 2021; 175: 113816
  • 4 Parthasarathy G, Hirsova P, Kostallari E, Sidhu GS, Ibrahim SH, Malhi H. Extracellular vesicles in hepatobiliary health and disease. Compr Physiol 2023; 13 (03) 4631-4658
  • 5 Thietart S, Rautou PE. Extracellular vesicles as biomarkers in liver diseases: a clinician's point of view. J Hepatol 2020; 73 (06) 1507-1525
  • 6 Welsh JA, Goberdhan DCI, O'Driscoll L. et al; MISEV Consortium. Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches. J Extracell Vesicles 2024; 13 (02) e12404
  • 7 Jeppesen DK, Zhang Q, Franklin JL, Coffey RJ. Extracellular vesicles and nanoparticles: emerging complexities. Trends Cell Biol 2023; 33 (08) 667-681
  • 8 Wang G, Li J, Bojmar L. et al. Tumour extracellular vesicles and particles induce liver metabolic dysfunction. Nature 2023; 618 (7964) 374-382
  • 9 Zhang H, Freitas D, Kim HS. et al. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat Cell Biol 2018; 20 (03) 332-343
  • 10 Ambros V. The functions of animal microRNAs. Nature 2004; 431 (7006) 350-355
  • 11 Chen Y, Wang X. miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Res 2020; 48 (D1): D127-D131
  • 12 Liu W, Wang X. Prediction of functional microRNA targets by integrative modeling of microRNA binding and target expression data. Genome Biol 2019; 20 (01) 18
  • 13 McGeary SE, Lin KS, Shi CY. et al. The biochemical basis of microRNA targeting efficacy. Science 2019; 366 (6472) 366
  • 14 Miranda KC, Huynh T, Tay Y. et al. A pattern-based method for the identification of microRNA binding sites and their corresponding heteroduplexes. Cell 2006; 126 (06) 1203-1217
  • 15 Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116 (02) 281-297
  • 16 Shang R, Lee S, Senavirathne G, Lai EC. microRNAs in action: biogenesis, function and regulation. Nat Rev Genet 2023; 24 (12) 816-833
  • 17 Treiber T, Treiber N, Meister G. Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nat Rev Mol Cell Biol 2019; 20 (01) 5-20
  • 18 Shurtleff MJ, Temoche-Diaz MM, Karfilis KV, Ri S, Schekman R. Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction. eLife 2016; 5: 5
  • 19 Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9 (06) 654-659
  • 20 Villarroya-Beltri C, Gutiérrez-Vázquez C, Sánchez-Cabo F. et al. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun 2013; 4: 2980
  • 21 Gibbings DJ, Ciaudo C, Erhardt M, Voinnet O. Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat Cell Biol 2009; 11 (09) 1143-1149
  • 22 McKenzie AJ, Hoshino D, Hong NH. et al. KRAS-MEK signaling controls Ago2 sorting into exosomes. Cell Rep 2016; 15 (05) 978-987
  • 23 Diaz LA, Winder GS, Leggio L, Bajaj JS, Bataller R, Arab JP. New insights into the molecular basis of alcohol abstinence and relapse in alcohol-associated liver disease. Hepatology 2023;
  • 24 Tan HK, Yates E, Lilly K, Dhanda AD. Oxidative stress in alcohol-related liver disease. World J Hepatol 2020; 12 (07) 332-349
  • 25 Bala S, Babuta M, Catalano D, Saiju A, Szabo G. Alcohol promotes exosome biogenesis and release via modulating Rabs and miR-192 expression in human hepatocytes. Front Cell Dev Biol 2022; 9: 787356
  • 26 Yu W, Wang S, Wang Y. et al. MicroRNA: role in macrophage polarization and the pathogenesis of the liver fibrosis. Front Immunol 2023; 14: 1147710
  • 27 Eguchi A, Lazaro RG, Wang J. et al. Extracellular vesicles released by hepatocytes from gastric infusion model of alcoholic liver disease contain a MicroRNA barcode that can be detected in blood. Hepatology 2017; 65 (02) 475-490
  • 28 Saha B, Momen-Heravi F, Furi I. et al. Extracellular vesicles from mice with alcoholic liver disease carry a distinct protein cargo and induce macrophage activation through heat shock protein 90. Hepatology 2018; 67 (05) 1986-2000
  • 29 Momen-Heravi F, Saha B, Kodys K, Catalano D, Satishchandran A, Szabo G. Increased number of circulating exosomes and their microRNA cargos are potential novel biomarkers in alcoholic hepatitis. J Transl Med 2015; 13: 261
  • 30 Bala S, Csak T, Saha B. et al. The pro-inflammatory effects of miR-155 promote liver fibrosis and alcohol-induced steatohepatitis. J Hepatol 2016; 64 (06) 1378-1387
  • 31 Bala S, Marcos M, Kodys K. et al. Up-regulation of microRNA-155 in macrophages contributes to increased tumor necrosis factor alpha (TNFalpha) production via increased mRNA half-life in alcoholic liver disease. J Biol Chem 2011; 286 (02) 1436-1444
  • 32 Babuta M, Furi I, Bala S. et al. Dysregulated autophagy and lysosome function are linked to exosome production by Micro-RNA 155 in alcoholic liver disease. Hepatology 2019; 70 (06) 2123-2141
  • 33 Saha B, Momen-Heravi F, Kodys K, Szabo G. MicroRNA cargo of extracellular vesicles from alcohol-exposed monocytes signals naive monocytes to differentiate into M2 macrophages. J Biol Chem 2016; 291 (01) 149-159
  • 34 Miao L, Targher G, Byrne CD, Cao YY, Zheng MH. Current status and future trends of the global burden of MASLD. Trends Endocrinol Metab 2024; 35 (08) 697-707
  • 35 Rinella ME, Lazarus JV, Ratziu V. et al; NAFLD Nomenclature consensus group. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol 2023; 79 (06) 1542-1556
  • 36 Ibrahim SH, Hirsova P, Gores GJ. Non-alcoholic steatohepatitis pathogenesis: sublethal hepatocyte injury as a driver of liver inflammation. Gut 2018; 67 (05) 963-972
  • 37 Atic AI, Thiele M, Munk A, Dalgaard LT. Circulating miRNAs associated with nonalcoholic fatty liver disease. Am J Physiol Cell Physiol 2023; 324 (02) C588-C602
  • 38 Mahmoudi A, Butler AE, Jamialahmadi T, Sahebkar A. The role of exosomal miRNA in nonalcoholic fatty liver disease. J Cell Physiol 2022; 237 (04) 2078-2094
  • 39 Wang X, He Y, Mackowiak B, Gao B. MicroRNAs as regulators, biomarkers and therapeutic targets in liver diseases. Gut 2021; 70 (04) 784-795
  • 40 Povero D, Panera N, Eguchi A. et al. Lipid-induced hepatocyte-derived extracellular vesicles regulate hepatic stellate cell via microRNAs targeting PPAR-γ. Cell Mol Gastroenterol Hepatol 2015; 1 (06) 646-663.e4
  • 41 Li Y, Luan Y, Li J. et al. Exosomal miR-199a-5p promotes hepatic lipid accumulation by modulating MST1 expression and fatty acid metabolism. Hepatol Int 2020; 14 (06) 1057-1074
  • 42 Jiang F, Chen Q, Wang W, Ling Y, Yan Y, Xia P. Hepatocyte-derived extracellular vesicles promote endothelial inflammation and atherogenesis via microRNA-1. J Hepatol 2020; 72 (01) 156-166
  • 43 Cai J, Zhang XJ, Li H. The role of innate immune cells in nonalcoholic steatohepatitis. Hepatology 2019; 70 (03) 1026-1037
  • 44 He Y, Rodrigues RM, Wang X. et al. Neutrophil-to-hepatocyte communication via LDLR-dependent miR-223-enriched extracellular vesicle transfer ameliorates nonalcoholic steatohepatitis. J Clin Invest 2021; 131 (03) 131
  • 45 Bandiera S, Pfeffer S, Baumert TF, Zeisel MB. miR-122–a key factor and therapeutic target in liver disease. J Hepatol 2015; 62 (02) 448-457
  • 46 Tsai WC, Hsu SD, Hsu CS. et al. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Invest 2012; 122 (08) 2884-2897
  • 47 Castaño C, Kalko S, Novials A, Párrizas M. Obesity-associated exosomal miRNAs modulate glucose and lipid metabolism in mice. Proc Natl Acad Sci U S A 2018; 115 (48) 12158-12163
  • 48 Chai C, Rivkin M, Berkovits L. et al. Metabolic circuit involving free fatty acids, microRNA 122, and triglyceride synthesis in liver and muscle tissues. Gastroenterology 2017; 153 (05) 1404-1415
  • 49 Chen K, Lin T, Yao W, Chen X, Xiong X, Huang Z. Adipocytes-derived exosomal miR-122 promotes non-alcoholic fat liver disease progression via targeting Sirt1. Gastroenterol Hepatol 2023; 46 (07) 531-541
  • 50 Jin X, Gao J, Zheng R. et al. Antagonizing circRNA_002581-miR-122-CPEB1 axis alleviates NASH through restoring PTEN-AMPK-mTOR pathway regulated autophagy. Cell Death Dis 2020; 11 (02) 123
  • 51 Higashi T, Friedman SL, Hoshida Y. Hepatic stellate cells as key target in liver fibrosis. Adv Drug Deliv Rev 2017; 121: 27-42
  • 52 Gao J, Wei B, de Assuncao TM. et al. Hepatic stellate cell autophagy inhibits extracellular vesicle release to attenuate liver fibrosis. J Hepatol 2020; 73 (05) 1144-1154
  • 53 Khanal S, Liu Y, Bamidele AO. et al. Glycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release spatially to amplify liver fibrosis. Sci Adv 2024; 10 (26) eadn5228
  • 54 Kostallari E, Hirsova P, Prasnicka A. et al. Hepatic stellate cell-derived platelet-derived growth factor receptor-alpha-enriched extracellular vesicles promote liver fibrosis in mice through SHP2. Hepatology 2018; 68 (01) 333-348
  • 55 Chen L, Charrier A, Zhou Y. et al. Epigenetic regulation of connective tissue growth factor by microRNA-214 delivery in exosomes from mouse or human hepatic stellate cells. Hepatology 2014; 59 (03) 1118-1129
  • 56 Kitano M, Bloomston PM. Hepatic Stellate Cells and microRNAs in Pathogenesis of Liver Fibrosis. J Clin Med 2016; 5 (03) 5
  • 57 Szabo G. Exosomes and microRNA-223 at the intersection of inflammation and fibrosis in NAFLD. Hepatology 2021; 74 (01) 5-8
  • 58 Chen L, Chen R, Velazquez VM, Brigstock DR. Fibrogenic signaling is suppressed in hepatic stellate cells through targeting of connective tissue growth factor (CCN2) by cellular or exosomal microRNA-199a-5p. Am J Pathol 2016; 186 (11) 2921-2933
  • 59 Tan J, Chen M, Liu M. et al. Exosomal miR-192-5p secreted by bone marrow mesenchymal stem cells inhibits hepatic stellate cell activation and targets PPP2R3A. J Histotechnol 2023; 46 (04) 158-169
  • 60 Niu Q, Wang T, Wang Z. et al. Adipose-derived mesenchymal stem cell-secreted extracellular vesicles alleviate non-alcoholic fatty liver disease via delivering miR-223-3p. Adipocyte 2022; 11 (01) 572-587
  • 61 Hou X, Yin S, Ren R. et al. Myeloid-cell-specific IL-6 signaling promotes microRNA-223-enriched exosome production to attenuate NAFLD-associated fibrosis. Hepatology 2021; 74 (01) 116-132
  • 62 Safran M, Masoud R, Sultan M. et al. Extracellular Vesicular transmission of miR-423-5p from HepG2 cells inhibits the differentiation of hepatic stellate cells. Cells 2022; 11 (10) 11
  • 63 Eguchi A, Yan R, Pan SQ. et al. Comprehensive characterization of hepatocyte-derived extracellular vesicles identifies direct miRNA-based regulation of hepatic stellate cells and DAMP-based hepatic macrophage IL-1β and IL-17 upregulation in alcoholic hepatitis mice. J Mol Med (Berl) 2020; 98 (07) 1021-1034
  • 64 Lee YS, Kim SY, Ko E. et al. Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells. Sci Rep 2017; 7 (01) 3710
  • 65 Chen L, Yao X, Yao H, Ji Q, Ding G, Liu X. Exosomal miR-103-3p from LPS-activated THP-1 macrophage contributes to the activation of hepatic stellate cells. FASEB J 2020; 34 (04) 5178-5192
  • 66 Lu H, Zhang R, Zhang S. et al. HSC-derived exosomal miR-199a-5p promotes HSC activation and hepatocyte EMT via targeting SIRT1 in hepatic fibrosis. Int Immunopharmacol 2023; 124 (Pt B): 111002
  • 67 Wang Y, Gong W, Zhou H. et al. A Novel miRNA from egg-derived exosomes of Schistosoma japonicum promotes liver fibrosis in murine schistosomiasis. Front Immunol 2022; 13: 860807
  • 68 He X, Wang Y, Fan X. et al. A schistosome miRNA promotes host hepatic fibrosis by targeting transforming growth factor beta receptor III. J Hepatol 2020; 72 (03) 519-527
  • 69 Yan C, Zhou QY, Wu J. et al. Csi-let-7a-5p delivered by extracellular vesicles from a liver fluke activates M1-like macrophages and exacerbates biliary injuries. Proc Natl Acad Sci U S A 2021; 118 (46) 118
  • 70 Augello G, Cusimano A, Cervello M, Cusimano A. Extracellular vesicle-related non-coding RNAs in hepatocellular carcinoma: an overview. Cancers (Basel) 2024; 16 (07) 16
  • 71 Seay TW, Suo Z. Roles of extracellular vesicles on the progression and metastasis of hepatocellular carcinoma. Cells 2023; 12 (14) 12
  • 72 Kogure T, Lin WL, Yan IK, Braconi C, Patel T. Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth. Hepatology 2011; 54 (04) 1237-1248
  • 73 Sun JF, Zhang D, Gao CJ, Zhang YW, Dai QS. Exosome-mediated MiR-155 transfer contributes to hepatocellular carcinoma cell proliferation by targeting PTEN. Med Sci Monit Basic Res 2019; 25: 218-228
  • 74 Liu J, Fan L, Yu H. et al. Endoplasmic reticulum stress causes liver cancer cells to release exosomal miR-23a-3p and up-regulate programmed death ligand 1 expression in macrophages. Hepatology 2019; 70 (01) 241-258
  • 75 Yin C, Han Q, Xu D, Zheng B, Zhao X, Zhang J. SALL4-mediated upregulation of exosomal miR-146a-5p drives T-cell exhaustion by M2 tumor-associated macrophages in HCC. OncoImmunology 2019; 8 (07) 1601479
  • 76 Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet 2019; 20 (11) 675-691
  • 77 Hu Z, Chen G, Zhao Y. et al. Exosome-derived circCCAR1 promotes CD8 + T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma. Mol Cancer 2023; 22 (01) 55
  • 78 Huang M, Huang X, Huang N. Exosomal circGSE1 promotes immune escape of hepatocellular carcinoma by inducing the expansion of regulatory T cells. Cancer Sci 2022; 113 (06) 1968-1983
  • 79 Lu JC, Zhang PF, Huang XY. et al. Amplification of spatially isolated adenosine pathway by tumor-macrophage interaction induces anti-PD1 resistance in hepatocellular carcinoma. J Hematol Oncol 2021; 14 (01) 200
  • 80 Matsuura Y, Wada H, Eguchi H. et al. Exosomal miR-155 Derived from hepatocellular carcinoma cells under hypoxia promotes angiogenesis in endothelial cells. Dig Dis Sci 2019; 64 (03) 792-802
  • 81 Wang X, Wang X, Xu M, Sheng W. Effects of CAF-derived microRNA on tumor biology and clinical applications. Cancers (Basel) 2021; 13 (13) 13
  • 82 Ying F, Chan MSM, Lee TKW. Cancer-associated fibroblasts in hepatocellular carcinoma and cholangiocarcinoma. Cell Mol Gastroenterol Hepatol 2023; 15 (04) 985-999
  • 83 Fang T, Lv H, Lv G. et al. Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer. Nat Commun 2018; 9 (01) 191
  • 84 Zhou Y, Ren H, Dai B. et al. Hepatocellular carcinoma-derived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts. J Exp Clin Cancer Res 2018; 37 (01) 324
  • 85 Zhou Y, Ren H, Dai B. et al. Correction: hepatocellular carcinoma-derived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts. J Exp Clin Cancer Res 2022; 41 (01) 359
  • 86 Wang F, Li L, Piontek K, Sakaguchi M, Selaru FM. Exosome miR-335 as a novel therapeutic strategy in hepatocellular carcinoma. Hepatology 2018; 67 (03) 940-954
  • 87 Tokuhisa A, Tsunedomi R, Kimura Y. et al. Exosomal miR-141-3p induces gemcitabine resistance in biliary tract cancer cells. Anticancer Res 2024; 44 (07) 2899-2908
  • 88 Wang J, Jiang W, Liu S. et al. Exosome-derived miR-182-5p promoted cholangiocarcinoma progression and vasculogenesis by regulating ADK/SEMA5a/PI3K pathway. Liver Int 2024; 44 (02) 370-388
  • 89 Luo C, Xin H, Zhou Z. et al. Tumor-derived exosomes induce immunosuppressive macrophages to foster intrahepatic cholangiocarcinoma progression. Hepatology 2022; 76 (04) 982-999
  • 90 Dong D, Yu X, Xu J, Yu N, Liu Z, Sun Y. Cellular and molecular mechanisms of gastrointestinal cancer liver metastases and drug resistance. Drug Resist Updat 2024; 77: 101125
  • 91 Chen Y, Lei Y, Li J, Wang X, Li G. Macrophage-derived exosomal microRNAs promote metastasis in pancreatic ductal adenocarcinoma. Int Immunopharmacol 2024; 129: 111590
  • 92 Lu F, Ye M, Shen Y. et al. Hypoxic tumor-derived exosomal miR-4488 induces macrophage M2 polarization to promote liver metastasis of pancreatic neuroendocrine neoplasm through RTN3/FABP5 mediated fatty acid oxidation. Int J Biol Sci 2024; 20 (08) 3201-3218
  • 93 Madhavan B, Yue S, Galli U. et al. Combined evaluation of a panel of protein and miRNA serum-exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity. Int J Cancer 2015; 136 (11) 2616-2627
  • 94 Hsu YL, Huang MS, Hung JY. et al. Bone-marrow-derived cell-released extracellular vesicle miR-92a regulates hepatic pre-metastatic niche in lung cancer. Oncogene 2020; 39 (04) 739-753
  • 95 Saraceni C, Birk J. A review of hepatitis B virus and hepatitis C virus immunopathogenesis. J Clin Transl Hepatol 2021; 9 (03) 409-418
  • 96 Liu M, Liu X, Pan M. et al. Characterization and microRNA expression analysis of serum-derived extracellular vesicles in severe liver injury from chronic HBV infection. Life (Basel) 2023; 13 (02) 13
  • 97 Chu Q, Li J, Chen J, Yuan Z. HBV induced the discharge of intrinsic antiviral miRNAs in HBV-replicating hepatocytes via extracellular vesicles to facilitate its replication. J Gen Virol 2022; 103 (05) 103
  • 98 Iacob DG, Rosca A, Ruta SM. Circulating microRNAs as non-invasive biomarkers for hepatitis B virus liver fibrosis. World J Gastroenterol 2020; 26 (11) 1113-1127
  • 99 Zhao X, Sun L, Mu T. et al. An HBV-encoded miRNA activates innate immunity to restrict HBV replication. J Mol Cell Biol 2020; 12 (04) 263-276
  • 100 Babuta M, Szabo G. Extracellular vesicles in inflammation: focus on the microRNA cargo of EVs in modulation of liver diseases. J Leukoc Biol 2022; 111 (01) 75-92
  • 101 Wu W, Wu D, Yan W. et al. Interferon-induced macrophage-derived exosomes mediate antiviral activity against hepatitis B virus through miR-574-5p. J Infect Dis 2021; 223 (04) 686-698
  • 102 You J, Wu W, Lu M. et al. Hepatic exosomes with declined MiR-27b-3p trigger RIG-I/TBK1 signal pathway in macrophages. Liver Int 2022; 42 (07) 1676-1691
  • 103 Kriegel AJ, Liu Y, Fang Y, Ding X, Liang M. The miR-29 family: genomics, cell biology, and relevance to renal and cardiovascular injury. Physiol Genomics 2012; 44 (04) 237-244
  • 104 Ullah A, Rehman IU, Ommer K. et al. Circulating miRNA-192 and miR-29a as disease progression biomarkers in hepatitis C patients with a prevalence of HCV genotype 3. Genes (Basel) 2023; 14 (05) 14
  • 105 Zhou Y, Wang X, Sun L. et al. Toll-like receptor 3-activated macrophages confer anti-HCV activity to hepatocytes through exosomes. FASEB J 2016; 30 (12) 4132-4140
  • 106 Ramakrishnaiah V, Thumann C, Fofana I. et al. Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells. Proc Natl Acad Sci U S A 2013; 110 (32) 13109-13113
  • 107 Santangelo L, Bordoni V, Montaldo C. et al. Hepatitis C virus direct-acting antivirals therapy impacts on extracellular vesicles microRNAs content and on their immunomodulating properties. Liver Int 2018; 38 (10) 1741-1750
  • 108 Devhare PB, Sasaki R, Shrivastava S. et al. Exosome-mediated intercellular communication between hepatitis C virus-infected hepatocytes and hepatic stellate cells. J Virol 2017; 91
  • 109 Eguchi A, Kostallari E, Feldstein AE, Shah VH. Extracellular vesicles, the liquid biopsy of the future. J Hepatol 2019; 70 (06) 1292-1294
  • 110 Bala S, Petrasek J, Mundkur S. et al. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 2012; 56 (05) 1946-1957
  • 111 Wang Z, Kim SY, Tu W. et al. Extracellular vesicles in fatty liver promote a metastatic tumor microenvironment. Cell Metab 2023; 35 (07) 1209-1226.e13
  • 112 Wan Z, Yang X, Liu X. et al. M2 macrophage-derived exosomal microRNA-411-5p impedes the activation of hepatic stellate cells by targeting CAMSAP1 in NASH model. iScience 2022; 25 (07) 104597
  • 113 Aghajanzadeh T, Talkhabi M, Zali MR, Hatami B, Baghaei K. Diagnostic potential and pathogenic performance of circulating miR-146b, miR-194, and miR-214 in liver fibrosis. Noncoding RNA Res 2023; 8 (04) 471-480
  • 114 Lambrecht J, Mannaerts I, van Grunsven LA. The role of miRNAs in stress-responsive hepatic stellate cells during liver fibrosis. Front Physiol 2015; 6: 209
  • 115 Zhang Y, Wu L, Wang Y. et al. Protective role of estrogen-induced miRNA-29 expression in carbon tetrachloride-induced mouse liver injury. J Biol Chem 2012; 287 (18) 14851-14862
  • 116 Lambrecht J, Jan Poortmans P, Verhulst S, Reynaert H, Mannaerts I, van Grunsven LA. Circulating ECV-associated miRNAs as potential clinical biomarkers in early stage HBV and HCV induced liver fibrosis. Front Pharmacol 2017; 8: 56
  • 117 Lee YT, Tran BV, Wang JJ. et al. The role of extracellular vesicles in disease progression and detection of hepatocellular carcinoma. Cancers (Basel) 2021; 13 (12) 13
  • 118 Lapitz A, Arbelaiz A, Olaizola P. et al. Extracellular vesicles in hepatobiliary malignancies. Front Immunol 2018; 9: 2270
  • 119 Mathew M, Zade M, Mezghani N, Patel R, Wang Y, Momen-Heravi F. Extracellular vesicles as biomarkers in cancer immunotherapy. Cancers (Basel) 2020; 12 (10) 12
  • 120 Szabo G, Momen-Heravi F. Extracellular vesicles in liver disease and potential as biomarkers and therapeutic targets. Nat Rev Gastroenterol Hepatol 2017; 14 (08) 455-466
  • 121 Mizenko RR, Feaver M, Bozkurt BT. et al. A critical systematic review of extracellular vesicle clinical trials. J Extracell Vesicles 2024; 13 (10) e12510
  • 122 Maji S, Matsuda A, Yan IK, Parasramka M, Patel T. Extracellular vesicles in liver diseases. Am J Physiol Gastrointest Liver Physiol 2017; 312 (03) G194-G200
  • 123 Povero D, Pinatel EM, Leszczynska A. et al. Human induced pluripotent stem cell-derived extracellular vesicles reduce hepatic stellate cell activation and liver fibrosis. JCI Insight 2019; 5 (14) 5
  • 124 Thakral S, Ghoshal K. miR-122 is a unique molecule with great potential in diagnosis, prognosis of liver disease, and therapy both as miRNA mimic and antimir. Curr Gene Ther 2015; 15 (02) 142-150
  • 125 Kim EH, Choi J, Jang H. et al. Targeted delivery of anti-miRNA21 sensitizes PD-L1high tumor to immunotherapy by promoting immunogenic cell death. Theranostics 2024; 14 (10) 3777-3792
  • 126 Yang YL, Chang YH, Li CJ. et al. New insights into the role of miR-29a in hepatocellular carcinoma: implications in mechanisms and theragnostics. J Pers Med 2021; 11 (03) 11
  • 127 Yu X, Elfimova N, Müller M. et al. Autophagy-related activation of hepatic stellate cells reduces cellular miR-29a by promoting its vesicular secretion. Cell Mol Gastroenterol Hepatol 2022; 13 (06) 1701-1716
  • 128 Li CJ, Fang QH, Liu ML, Lin JN. Current understanding of the role of adipose-derived extracellular vesicles in metabolic homeostasis and diseases: communication from the distance between cells/tissues. Theranostics 2020; 10 (16) 7422-7435
  • 129 Ying W, Riopel M, Bandyopadhyay G. et al. Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity. Cell 2017; 171 (02) 372-384.e12