Role of exosomes in the development, progression, diagnosis, and treatment of liver fibrosis

Yehao LUO; Qiuxia CHEN; Ting LYU; Peiqi OU; Zhiyong CAO; Xuelin DUAN

doi:10.3969/j.issn.1001-5256.2021.12.038

Volume 37 Issue 12

Dec. 2021

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2021 > 37(12): 2919-2923

PDF( 2707 KB)

Role of exosomes in the development, progression, diagnosis, and treatment of liver fibrosis

DOI: 10.3969/j.issn.1001-5256.2021.12.038

1.
Key Laboratory of Zhuang Medicine Prescriptions Basis and Application Research, Guangxi University of Chinese Medicine, Nanning 530200, China
2.
School of Medicine, Hubei Minzu University, Enshi, Hubei 445000, China

Research funding:

University-Level First-Class Discipline Construction Open Subject Project (2019XK040)

Received Date: 2021-04-26
Accepted Date: 2021-06-13
Published Date: 2021-12-20

Abstract

Abstract

An increasing number of studies have demonstrated that exosomes are closely associated with liver fibrosis and mediate the process of liver fibrosis by participating in cytokine secretion, macrophage activation, extracellular matrix remodeling, and hepatic stellate cell activation. This article summarizes that the resolution of liver fibrosis requires the reduction of pro-inflammatory and fibrotic cytokines, the reduction of extracellular matrix protein production, the increase of collagenase activity, and finally the loss of activated myofibroblasts. It is believed that exosomes play an important role in the treatment of liver fibrosis and are potential markers for diagnosis and treatment, and in future studies, it is necessary to improve exosome extraction techniques and standardization of treatment quantification.
- Liver Cirrhosis,
- Exosomes,
- Pathologic Processes,
- Diagnosis,
- Therapeutics

FullText(HTML)

References(48)

References

[1]	DHAR D, BAGLIERI J, KISSELEVA T, et al. Mechanisms of liver fibrosis and its role in liver cancer[J]. Exp Biol Med (Maywood), 2020, 245(2): 96-108. DOI: 10.1177/1535370219898141.
[2]	PAROLA M, PINZANI M. Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues[J]. Mol Aspects Med, 2019, 65: 37-55. DOI: 10.1016/j.mam.2018.09.002.
[3]	ŠMÍD V. Liver fibrosis[J]. Vnitr Lek, 2020, 66(4): 61-66.
[4]	ALZHRANI GN, ALANAZI ST, ALSHARIF SY, et al. Exosomes: Isolation, characterization, and biomedical applications[J]. Cell Biol Int, 2021, 45(9): 1807-1831. DOI: 10.1002/cbin.11620.
[5]	ALSHEHRI B. Plant-derived xenomiRs and cancer: Cross-kingdom gene regulation[J]. Saudi J Biol Sci, 2021, 28(4): 2408-2422. DOI: 10.1016/j.sjbs.2021.01.039.
[6]	LIU MY, FU L, ZHANG WH, et al. Progress in mechanism of interaction between immune cells and exosomes[J]. Chin J Immunol, 2019, 35(22): 2806-2812. DOI: 10.3969/j.issn.1000-484X.2019.22.024. 刘满宇, 付璐, 张文慧, 等. 免疫细胞与外泌体相互作用机制的研究进展[J]. 中国免疫学杂志, 2019, 35(22): 2806-2812. DOI: 10.3969/j.issn.1000-484X.2019.22.024.
[7]	DEWIDAR B, MEYER C, DOOLEY S, et al. TGF-β in hepatic stellate cell activation and liver fibrogenesis-updated 2019[J]. Cells, 2019, 8(11): 1419. DOI: 10.3390/cells8111419.
[8]	WEISKIRCHEN R, WEISKIRCHEN S, TACKE F. Organ and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications[J]. Mol Aspects Med, 2019, 65: 2-15. DOI: 10.1016/j.mam.2018.06.003.
[9]	FUENTES-CALVO I, MARTINEZ-SALGADO C. Sos1 modulates extracellular matrix synthesis, proliferation, and migration in fibroblasts[J]. Front Physiol, 2021, 12: 645044. DOI: 10.3389/fphys.2021.645044.
[10]	KIM J, KANG W, KANG SH, et al. Proline-rich tyrosine kinase 2 mediates transforming growth factor-beta-induced hepatic stellate cell activation and liver fibrosis[J]. Sci Rep, 2020, 10(1): 21018. DOI: 10.1038/s41598-020-78056-0.
[11]	CHEN PJ, KUO LM, WU YH, et al. BAY 41-2272 attenuates CTGF expression via sGC/cGMP-independent pathway in TGFβ1-activated hepatic stellate cells[J]. Biomedicines, 2020, 8(9): 330. DOI: 10.3390/biomedicines8090330.
[12]	SHAO J, LI S, LIU Y, et al. Extracellular vesicles participate in macrophage-involved immune responses under liver diseases[J]. Life Sci, 2020, 240: 117094. DOI: 10.1016/j.lfs.2019.117094.
[13]	SHEN M, SHEN Y, FAN X, et al. Roles of macrophages and exosomes in liver diseases[J]. Front Med (Lausanne), 2020, 7: 583691. DOI: 10.3389/fmed.2020.583691.
[14]	AN SY, PETRESCU AD, DEMORROW S. Targeting certain interleukins as novel treatment options for liver fibrosis[J]. Front Pharmacol, 2021, 12: 645703. DOI: 10.3389/fphar.2021.645703.
[15]	DEGROOTE H, LEFERE S, VANDIERENDONCK A, et al. Characterization of the inflammatory microenvironment and hepatic macrophage subsets in experimental hepatocellular carcinoma models[J]. Oncotarget, 2021, 12(6): 562-577. DOI: 10.18632/oncotarget.27906.
[16]	ROEHLEN N, CROUCHET E, BAUMERT TF. Liver fibrosis: Mechanistic concepts and therapeutic perspectives[J]. Cells, 2020, 9(4): 875. DOI: 10.3390/cells9040875.
[17]	PINHEIRO D, DIAS I, RIBEIRO SILVA K, et al. Mechanisms underlying cell therapy in liver fibrosis: An overview[J]. Cells, 2019, 8(11): 1339. DOI: 10.3390/cells8111339.
[18]	WANG JP, LI TZ, HUANG XY, et al. Synthesis and anti-fibrotic effects of santamarin derivatives as cytotoxic agents against hepatic stellate cell line LX2[J]. Bioorg Med Chem Lett, 2021, 41: 127994. DOI: 10.1016/j.bmcl.2021.127994.
[19]	SHU Y, LIU X, HUANG H, et al. Research progress of natural compounds in anti-liver fibrosis by affecting autophagy of hepatic stellate cells[J]. Mol Biol Rep, 2021, 48(2): 1915-1924. DOI: 10.1007/s11033-021-06171-w.
[20]	HOFFMANN C, DJERIR N, DANCKAERT A, et al. Hepatic stellate cell hypertrophy is associated with metabolic liver fibrosis[J]. Sci Rep, 2020, 10(1): 3850. DOI: 10.1038/s41598-020-60615-0.
[21]	KHOMICH O, IVANOV AV, BARTOSCH B. Metabolic hallmarks of hepatic stellate cells in liver fibrosis[J]. Cells, 2019, 9(1): 24. DOI: 10.3390/cells9010024.
[22]	CHEN Z, JAIN A, LIU H, et al. Targeted drug delivery to hepatic stellate cells for the treatment of liver fibrosis[J]. J Pharmacol Exp Ther, 2019, 370(3): 695-702. DOI: 10.1124/jpet.118.256156.
[23]	WANG X, SEO W, PARK SH, et al. MicroRNA-223 restricts liver fibrosis by inhibiting the TAZ-IHH-GLI2 and PDGF signaling pathways via the crosstalk of multiple liver cell types[J]. Int J Biol Sci, 2021, 17(4): 1153-1167. DOI: 10.7150/ijbs.58365.
[24]	HAN Z, MA Y, CAO G, et al. Integrin αVβ1 regulates procollagen I production through a non-canonical transforming growth factor β signaling pathway in human hepatic stellate cells[J]. Biochem J, 2021, 478(9): 1689-1703. DOI: 10.1042/BCJ20200749.
[25]	ZENOVIA S, STANCIU C, SFARTI C, et al. Vibration-controlled transient elastography and controlled attenuation parameter for the diagnosis of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease[J]. Diagnostics (Basel), 2021, 11(5): 787. DOI: 10.3390/diagnostics11050787.
[26]	FLAMINI S, SERGEEV P, VIANA DE BARROS Z, et al. Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment[J]. Cell Death Dis, 2021, 12(5): 421. DOI: 10.1038/s41419-021-03704-w.
[27]	LIN CY, ADHIKARY P, CHENG K. Cellular protein markers, therapeutics, and drug delivery strategies in the treatment of diabetes-associated liver fibrosis[J]. Adv Drug Deliv Rev, 2021, 174: 127-139. DOI: 10.1016/j.addr.2021.04.008.
[28]	GANTUMUR D, HARIMOTO N, MURANUSHI R, et al. Hepatic stellate cell as a Mac-2-binding protein-producing cell in patients with liver fibrosis[J]. Hepatol Res, 2021. DOI: 10.1111/hepr.13648.[Online ahead of print]
[29]	ZHAO Z, LIN CY, CHENG K. siRNA- and miRNA-based therapeutics for liver fibrosis[J]. Transl Res, 2019, 214: 17-29. DOI: 10.1016/j.trsl.2019.07.007.
[30]	YIN F, WANG WY, JIANG WH. Human umbilical cord mesenchymal stem cells ameliorate liver fibrosis in vitro and in vivo: From biological characteristics to therapeutic mechanisms[J]. World J Stem Cells, 2019, 11(8): 548-564. DOI: 10.4252/wjsc.v11.i8.548.
[31]	LUCANTONI F, MARTÍNEZ-CEREZUELA A, GRUEVSKA A, et al. Understanding the implication of autophagy in the activation of hepatic stellate cells in liver fibrosis: Are we there yet?[J]. J Pathol, 2021, 254(3): 216-228. DOI: 10.1002/path.5678.
[32]	SUN XH, ZHANG H, FAN XP, et al. Astilbin protects against carbon tetrachloride-induced liver fibrosis in rats[J]. Pharmacology, 2021, 106(5-6): 323-331. DOI: 10.1159/000514594.
[33]	WANG L, WANG Y, QUAN J. Exosomes derived from natural killer cells inhibit hepatic stellate cell activation and liver fibrosis[J]. Hum Cell, 2020, 33(3): 582-589. DOI: 10.1007/s13577-020-00371-5.
[34]	GAO J, WEI B, de ASSUNCAO TM, et al. Hepatic stellate cell autophagy inhibits extracellular vesicle release to attenuate liver fibrosis[J]. J Hepatol, 2020, 73(5): 1144-1154. DOI: 10.1016/j.jhep.2020.04.044.
[35]	ZHANG XW, ZHOU JC, PENG D, et al. Disrupting the TRIB3-SQSTM1 interaction reduces liver fibrosis by restoring autophagy and suppressing exosome-mediated HSC activation[J]. Autophagy, 2020, 16(5): 782-796. DOI: 10.1080/15548627.2019.1635383.
[36]	HODGE A, ANDREWARTHA N, LOURENSZ D, et al. Human amnion epithelial cells produce soluble factors that enhance liver repair by reducing fibrosis while maintaining regeneration in a model of chronic liver injury[J]. Cell Transplant, 2020, 29: 963689720950221. DOI: 10.1177/0963689720950221.
[37]	ALATAS FS, MATSUURA T, PUDJIADI AH, et al. Peroxisome proliferator-activated receptor gamma agonist attenuates liver fibrosis by several fibrogenic pathways in an animal model of cholestatic fibrosis[J]. Pediatr Gastroenterol Hepatol Nutr, 2020, 23(4): 346-355. DOI: 10.5223/pghn.2020.23.4.346.
[38]	YANG X, MA L, WEI R, et al. Twist1-induced miR-199a-3p promotes liver fibrosis by suppressing caveolin-2 and activating TGF-β pathway[J]. Signal Transduct Target Ther, 2020, 5(1): 75. DOI: 10.1038/s41392-020-0169-z.
[39]	KISSELEVA T, BRENNER D. Molecular and cellular mechanisms of liver fibrosis and its regression[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(3): 151-166. DOI: 10.1038/s41575-020-00372-7.
[40]	RONG X, LIU J, YAO X, et al. Human bone marrow mesenchymal stem cells-derived exosomes alleviate liver fibrosis through the Wnt/β-catenin pathway[J]. Stem Cell Res Ther, 2019, 10(1): 98. DOI: 10.1186/s13287-019-1204-2.
[41]	WATANABE Y, TSUCHIYA A, SEINO S, et al. Mesenchymal stem cells and induced bone marrow-derived macrophages synergistically improve liver fibrosis in mice[J]. Stem Cells Transl Med, 2019, 8(3): 271-284. DOI: 10.1002/sctm.18-0105.
[42]	CHEN L, CHEN R, 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.
[43]	JIAO Y, XU P, SHI H, et al. Advances on liver cell-derived exosomes in liver diseases[J]. J Cell Mol Med, 2021, 25(1): 15-26. DOI: 10.1111/jcmm.16123.
[44]	CIFERRI MC, QUARTO R, TASSO R. Extracellular vesicles as biomarkers and therapeutic tools: From pre-clinical to clinical applications[J]. Biology (Basel), 2021, 10(5): 359. DOI: 10.3390/biology10050359.
[45]	EUDY BJ, MCDERMOTT CE, LIU X, et al. Targeted and untargeted metabolomics provide insight into the consequences of glycine-N-methyltransferase deficiency including the novel finding of defective immune function[J]. Physiol Rep, 2020, 8(18): e14576. DOI: 10.14814/phy2.14576.
[46]	ZHANG Q, ZHANG Q, LI B, et al. The diagnosis value of a novel model with 5 circulating miRNAs for liver fibrosis in patients with chronic hepatitis B[J]. Mediators Inflamm, 2021, 2021: 6636947. DOI: 10.1155/2021/6636947.
[47]	ZHAO Z, ZHONG L, LI P, et al. Cholesterol impairs hepatocyte lysosomal function causing M1 polarization of macrophages via exosomal miR-122-5p[J]. Exp Cell Res, 2020, 387(1): 111738. DOI: 10.1016/j.yexcr.2019.111738.
[48]	SHEN M, SHEN Y, FAN X, et al. Roles of macrophages and exosomes in liver diseases[J]. Front Med (Lausanne), 2020, 7: 583691. DOI: 10.3389/fmed.2020.583691.

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

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

Figures(2)

Get Citation

PDF

XML

Article Metrics

Article views (854) PDF downloads(62)

Role of exosomes in the development, progression, diagnosis, and treatment of liver fibrosis

DOI: 10.3969/j.issn.1001-5256.2021.12.038

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Role of exosomes in the development, progression, diagnosis, and treatment of liver fibrosis

DOI: 10.3969/j.issn.1001-5256.2021.12.038

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content