The Role of Extracellular Vesicles in Liver Fibrosis: Friends or Foes?

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2025 Jan 8

PMID 39767572

Authors

Xiang Tao

Can Chen

Mei Liu

Affiliations

Soon will be listed here.

Abstract

Liver fibrosis represents a common pathway in the progression of various chronic liver diseases towards cirrhosis and liver failure. Extracellular vesicles (EVs) are membrane-enclosed particles secreted by diverse cell types, including exosomes, microvesicles, apoptotic vesicles, and the recently identified migrasomes. These vesicles can be taken up by recipient cells, thereby modulating their function through the transport of cargo molecules. EVs facilitate intercellular communication and play a significant role in the development of liver fibrosis. Moreover, the detection of EVs in various body fluids offers sensitive diagnostic tools for assessing liver fibrosis. Additionally, EVs may serve as therapeutic targets, potential therapeutic agents, and drug delivery vehicles. This article reviews recent advances in the field of EVs concerning liver fibrosis and related diseases, with a particular focus on the potential role of the newly discovered migrasomes in intracellular crosstalk within the liver.

References

Sun C, Shi C, Duan X, Zhang Y, Wang B . Exosomal microRNA-618 derived from mesenchymal stem cells attenuate the progression of hepatic fibrosis by targeting Smad4. Bioengineered. 2022; 13(3):5915-5927. PMC: 8973762. DOI: 10.1080/21655979.2021.2023799. View

Li Y, Wu J, Liu R, Zhang Y, Li X . Extracellular vesicles: catching the light of intercellular communication in fibrotic liver diseases. Theranostics. 2022; 12(16):6955-6971. PMC: 9576620. DOI: 10.7150/thno.77256. View

Krishnan S, Bebawy M . Circulating biosignatures in multiple myeloma and their role in multidrug resistance. Mol Cancer. 2023; 22(1):79. PMC: 10148481. DOI: 10.1186/s12943-022-01683-w. View

Wan L, Xia T, Du Y, Liu J, Xie Y, Zhang Y . Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exosomes in metabolic switch of liver nonparenchymal cells. FASEB J. 2019; 33(7):8530-8542. DOI: 10.1096/fj.201802675R. View

Takeda N, Tsuchiya A, Mito M, Natsui K, Natusi Y, Koseki Y . Analysis of distribution, collection, and confirmation of capacity dependency of small extracellular vesicles toward a therapy for liver cirrhosis. Inflamm Regen. 2023; 43(1):48. PMC: 10561446. DOI: 10.1186/s41232-023-00299-x. View

Kisseleva T, Brenner D . Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol. 2020; 18(3):151-166. DOI: 10.1038/s41575-020-00372-7. View

Gong L, Zhou H, Zhang S, Wang C, Fu K, Ma C . CD44-Targeting Drug Delivery System of Exosomes Loading Forsythiaside A Combats Liver Fibrosis via Regulating NLRP3-Mediated Pyroptosis. Adv Healthc Mater. 2023; 12(11):e2202228. DOI: 10.1002/adhm.202202228. View

Zhang R, Peng J, Zhang Y, Zheng K, Chen Y, Liu L . Pancreatic cancer cell-derived migrasomes promote cancer progression by fostering an immunosuppressive tumor microenvironment. Cancer Lett. 2024; 605:217289. DOI: 10.1016/j.canlet.2024.217289. View

Elkrief L, Ganne-Carrie N, Manceau H, Tanguy M, Valainathan S, Riescher-Tuczkiewicz A . Hepatocyte-derived biomarkers predict liver-related events at 2 years in Child-Pugh class A alcohol-related cirrhosis. J Hepatol. 2023; 79(4):910-923. DOI: 10.1016/j.jhep.2023.05.025. View

10.

Li Y, Liu R, Ding M, Zheng Q, Wu J, Xue X . Tetramethylpyrazine prevents liver fibrotic injury in mice by targeting hepatocyte-derived and mitochondrial DNA-enriched extracellular vesicles. Acta Pharmacol Sin. 2022; 43(8):2026-2041. PMC: 9343419. DOI: 10.1038/s41401-021-00843-w. View

11.

Kostallari E, Valainathan S, Biquard L, Shah V, Rautou P . Role of extracellular vesicles in liver diseases and their therapeutic potential. Adv Drug Deliv Rev. 2021; 175:113816. PMC: 10798367. DOI: 10.1016/j.addr.2021.05.026. View

12.

Zhu D, Sun Z, Wei J, Zhang Y, An W, Lin Y . BMP7-Loaded Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Ameliorate Liver Fibrosis by Targeting Activated Hepatic Stellate Cells. Int J Nanomedicine. 2024; 19:3475-3495. PMC: 11018131. DOI: 10.2147/IJN.S450284. View

13.

Thietart S, Rautou P . Extracellular vesicles as biomarkers in liver diseases: A clinician's point of view. J Hepatol. 2020; 73(6):1507-1525. DOI: 10.1016/j.jhep.2020.07.014. View

14.

Pastore M, Caligiuri A, Raggi C, Navari N, Piombanti B, Maira G . Macrophage MerTK promotes profibrogenic cross-talk with hepatic stellate cells via soluble mediators. JHEP Rep. 2022; 4(4):100444. PMC: 8891698. DOI: 10.1016/j.jhepr.2022.100444. View

15.

Wu J, Lu Z, Jiang D, Guo Y, Qiao H, Zhang Y . Iterative tomography with digital adaptive optics permits hour-long intravital observation of 3D subcellular dynamics at millisecond scale. Cell. 2021; 184(12):3318-3332.e17. DOI: 10.1016/j.cell.2021.04.029. View

16.

Li T, Su X, Lu P, Kang X, Hu M, Li C . Bone Marrow Mesenchymal Stem Cell-Derived Dermcidin-Containing Migrasomes enhance LC3-Associated Phagocytosis of Pulmonary Macrophages and Protect against Post-Stroke Pneumonia. Adv Sci (Weinh). 2023; 10(22):e2206432. PMC: 10401184. DOI: 10.1002/advs.202206432. View

17.

Momen-Heravi F, Getting S, Moschos S . Extracellular vesicles and their nucleic acids for biomarker discovery. Pharmacol Ther. 2018; 192:170-187. DOI: 10.1016/j.pharmthera.2018.08.002. View

18.

Zheng W, Bian S, Qiu S, Bishop C, Wan M, Xu N . Placenta mesenchymal stem cell-derived extracellular vesicles alleviate liver fibrosis by inactivating hepatic stellate cells through a miR-378c/SKP2 axis. Inflamm Regen. 2023; 43(1):47. PMC: 10557276. DOI: 10.1186/s41232-023-00297-z. View

19.

Sakane S, Hikita H, Shirai K, Sakamoto T, Narumi R, Adachi J . Proteomic analysis of serum extracellular vesicles reveals Fibulin-3 as a new marker predicting liver-related events in MASLD. Hepatol Commun. 2024; 8(6). PMC: 11150025. DOI: 10.1097/HC9.0000000000000448. View

20.

Li G, Zhao Y, Wang H, Zhang Y, Cai D, Zhang Y . The M2 Macrophages Derived Migrasomes From the Surface of Titania Nanotubes Array as a New Concept for Enhancing Osteogenesis. Adv Healthc Mater. 2024; 13(20):e2400257. DOI: 10.1002/adhm.202400257. View