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Hepatology International
Erschienen in: Hepatology International 4/2023

13.04.2023 | Original Article

Liver-derived extracellular vesicles from patients with hepatitis B virus-related acute-on-chronic liver failure impair hepatic regeneration by inhibiting on FGFR2 signaling via miR-218-5p

verfasst von: Senquan Zhang, Jie Yu, Keqiang Rao, Jie Cao, Lijie Ma, Yeping Yu, Zhe Li, Zhaokai Zeng, Yongbing Qian, Mo Chen, Hualian Hang

Erschienen in: Hepatology International | Ausgabe 4/2023

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Abstract

Background

Impaired liver regeneration in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients is closely related to prognosis; however, the mechanisms are not yet defined. Liver-derived extracellular vesicles (EVs) may be involved in the dysregulation of liver regeneration. Clarifying the underlying mechanisms will improve the treatments for HBV-ACLF.

Methods

EVs were isolated by ultracentrifugation from liver tissues of HBV-ACLF patients (ACLF_EVs) after liver transplantation, and their function was investigated in acute liver injury (ALI) mice and AML12 cells. Differentially expressed miRNAs (DE-miRNAs) were screened by deep miRNA sequencing. The lipid nanoparticle (LNP) system was applied as a carrier for the targeted delivery of miRNA inhibitors to improve its effect on liver regeneration.

Results

ACLF_EVs inhibited hepatocyte proliferation and liver regeneration, with a critical role of miR-218-5p. Mechanistically, ACLF_EVs fused directly with target hepatocytes and transferred miR-218-5p into hepatocytes, acting by suppressing FGFR2 mRNA and inhibiting the activation of ERK1/2 signaling pathway. Reducing the level of miR-218-5p expression in the liver of ACLF mice partially restored liver regeneration ability.

Conclusion

The current data reveal the mechanism underlying impaired liver regeneration in HBV-ACLF that promotes the discovery of new therapeutic approaches.

Graphical abstract

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Metadaten
Titel
Liver-derived extracellular vesicles from patients with hepatitis B virus-related acute-on-chronic liver failure impair hepatic regeneration by inhibiting on FGFR2 signaling via miR-218-5p
verfasst von
Senquan Zhang
Jie Yu
Keqiang Rao
Jie Cao
Lijie Ma
Yeping Yu
Zhe Li
Zhaokai Zeng
Yongbing Qian
Mo Chen
Hualian Hang
Publikationsdatum
13.04.2023
Verlag
Springer India
Erschienen in
Hepatology International / Ausgabe 4/2023
Print ISSN: 1936-0533
Elektronische ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-023-10513-0

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