Role of Exosomes in Chronic Liver Disease Development and Their Potential Clinical Applications

Overview

Journal J Immunol Res

Publisher Wiley

Specialty Allergy & Immunology

Date 2022 May 16

PMID 35571570

Authors

Chen Wang

Jinwen Liu

Yongmin Yan

Youwen Tan

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EVs) are vesicular bodies (40-1000 nm) with double-layer membrane structures released by different cell types into extracellular environments, including apoptosis bodies, microvesicles, and exosomes. Exosomes (30-100 nm) are vesicles enclosed by extracellular membrane and contain effective molecules of secretory cells. They are derived from intracellular multivesicular bodies (MVBs) that fuse with the plasma membrane and release their intracellular vesicles by exocytosis. Research has shown that almost all human cells could secrete exosomes, which have a certain relationship with corresponding diseases. In chronic liver diseases, exosomes release a variety of bioactive components into extracellular spaces, mediating intercellular signal transduction and materials transport. Moreover, exosomes play a role in the diagnosis, treatment, and prognosis of various chronic liver diseases as potential biomarkers and therapeutic targets. Previous studies have found that mesenchymal stem cell-derived exosomes (MSC-ex) could alleviate acute and chronic liver injury and have the advantages of high biocompatibility and low immunogenicity. In this paper, we briefly summarize the role of exosomes in the pathogenesis of different chronic liver diseases and the latest research progresses of MSC-ex as the clinical therapeutic targets.

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References

Csak T, Bala S, Lippai D, Satishchandran A, Catalano D, Kodys K . microRNA-122 regulates hypoxia-inducible factor-1 and vimentin in hepatocytes and correlates with fibrosis in diet-induced steatohepatitis. Liver Int. 2014; 35(2):532-41. PMC: 4289469. DOI: 10.1111/liv.12633. View

Cui Y, Xu H, Liu M, Xu Y, He J, Zhou Y . Mechanism of exosomal microRNA-224 in development of hepatocellular carcinoma and its diagnostic and prognostic value. World J Gastroenterol. 2019; 25(15):1890-1898. PMC: 6478613. DOI: 10.3748/wjg.v25.i15.1890. View

Lin Q, Zhou C, Bai M, Zhu D, Chen J, Wang H . Exosome-mediated miRNA delivery promotes liver cancer EMT and metastasis. Am J Transl Res. 2020; 12(3):1080-1095. PMC: 7137059. View

Zhou W, Zhang Q, Qiao L . Pathogenesis of liver cirrhosis. World J Gastroenterol. 2014; 20(23):7312-24. PMC: 4064077. DOI: 10.3748/wjg.v20.i23.7312. View

Eguchi A, Yan R, Pan S, Wu R, Kim J, Chen Y . 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(7):1021-1034. PMC: 7810220. DOI: 10.1007/s00109-020-01926-7. View

Nakano T, Chen I, Wang C, Chen P, Tseng H, Huang K . Circulating exosomal miR-92b: Its role for cancer immunoediting and clinical value for prediction of posttransplant hepatocellular carcinoma recurrence. Am J Transplant. 2019; 19(12):3250-3262. DOI: 10.1111/ajt.15490. View

Jiao Y, Xu P, Shi H, Chen D, Shi H . Advances on liver cell-derived exosomes in liver diseases. J Cell Mol Med. 2020; 25(1):15-26. PMC: 7810930. DOI: 10.1111/jcmm.16123. View

Joseph J, Harishankar M, Pillai A, Devi A . Hypoxia induced EMT: A review on the mechanism of tumor progression and metastasis in OSCC. Oral Oncol. 2018; 80:23-32. DOI: 10.1016/j.oraloncology.2018.03.004. View

Hirsova P, Ibrahim S, Krishnan A, Verma V, Bronk S, Werneburg N . Lipid-Induced Signaling Causes Release of Inflammatory Extracellular Vesicles From Hepatocytes. Gastroenterology. 2016; 150(4):956-67. PMC: 4808464. DOI: 10.1053/j.gastro.2015.12.037. View

10.

Sugimachi K, Matsumura T, Hirata H, Uchi R, Ueda M, Ueo H . Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation. Br J Cancer. 2015; 112(3):532-8. PMC: 4453648. DOI: 10.1038/bjc.2014.621. View

11.

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. PMC: 4533956. DOI: 10.1186/s12967-015-0623-9. View

12.

Thomou T, Mori M, Dreyfuss J, Konishi M, Sakaguchi M, Wolfrum C . Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature. 2017; 542(7642):450-455. PMC: 5330251. DOI: 10.1038/nature21365. View

13.

Qu Z, Feng J, Pan H, Jiang Y, Duan Y, Fa Z . Exosomes derived from HCC cells with different invasion characteristics mediated EMT through TGF-β/Smad signaling pathway. Onco Targets Ther. 2019; 12:6897-6905. PMC: 6711569. DOI: 10.2147/OTT.S209413. View

14.

Povero D, Eguchi A, Li H, Johnson C, Papouchado B, Wree A . Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease. PLoS One. 2014; 9(12):e113651. PMC: 4254757. DOI: 10.1371/journal.pone.0113651. View

15.

Ibrahim S, Hirsova P, Gores G . Non-alcoholic steatohepatitis pathogenesis: sublethal hepatocyte injury as a driver of liver inflammation. Gut. 2018; 67(5):963-972. PMC: 5889737. DOI: 10.1136/gutjnl-2017-315691. View

16.

Lamas-Paz A, Moran L, Peng J, Salinas B, Lopez-Alcantara N, Sydor S . Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury. Front Pharmacol. 2021; 11:603771. PMC: 7779758. DOI: 10.3389/fphar.2020.603771. View

17.

Chen L, Chen R, Kemper S, Cong M, You H, Brigstock D . Therapeutic effects of serum extracellular vesicles in liver fibrosis. J Extracell Vesicles. 2018; 7(1):1461505. PMC: 5912192. DOI: 10.1080/20013078.2018.1461505. View

18.

Li Y, Luan Y, Li J, Song H, Li Y, Qi H . Exosomal miR-199a-5p promotes hepatic lipid accumulation by modulating MST1 expression and fatty acid metabolism. Hepatol Int. 2020; 14(6):1057-1074. DOI: 10.1007/s12072-020-10096-0. View

19.

Cobbina E, Akhlaghi F . Non-alcoholic fatty liver disease (NAFLD) - pathogenesis, classification, and effect on drug metabolizing enzymes and transporters. Drug Metab Rev. 2017; 49(2):197-211. PMC: 5576152. DOI: 10.1080/03602532.2017.1293683. View

20.

Ban L, Shackel N, McLennan S . Extracellular Vesicles: A New Frontier in Biomarker Discovery for Non-Alcoholic Fatty Liver Disease. Int J Mol Sci. 2016; 17(3):376. PMC: 4813235. DOI: 10.3390/ijms17030376. View