Cited by 70Extracellular vesicles in diseaseLiver Disease Diagnosis and TreatmentMicroRNA in disease regulation

Adipose-derived mesenchymal stem cell-secreted extracellular vesicles alleviate non-alcoholic fatty liver disease via delivering miR-223-3p

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Niu, Qinghui, Wang, Ting, Wang, Zhiqiang, Wang, Feng, Huang, Deyu, Sun, Huali, Liu, Hanyun·2022·Adipocyte

Abstract

Increasing studies have identified the potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in non-alcoholic fatty liver disease (NAFLD) treatment. Hence, we further focused on the potential of adipose-derived MSC (ADSC)-EVs in NAFLD by delivering miR-223-3p. The uptake of isolated ADSC-EVs by hepatocytes was assessed, and the expression of miR-223-3p in ADSC-EVs and hepatocytes was characterized. It was established that miR-223-3p, enriched in ADSC-EVs, could be delivered by ADSC-EVs into hepatocytes. Using co-culture system and gain-of-function approach, we evaluated the effect of ADSC-EVs carrying miR-223-3p on lipid accumulation and liver fibrosis in pyrrolizidine alkaloids (PA)-induced hepatocytes and a high-fat diet-induced NAFLD mouse model. Bioinformatics websites and dual-luciferase reporter gene assay were performed to determine the interactions between miR-223-3p and E2F1, which was further validated by rescue experiments. ADSC-EVs containing miR-223-3p displayed suppressive effects on lipid accumulation and liver fibrosis through E2F1 inhibition, since E2F1 was demonstrated as a target gene of miR-223-3p. The protective role of ADSC-EVs by delivering miR-223-3p was then confirmed in the mouse model. Collectively, this study elucidated that ADSC-EVs delayed the progression NAFLD through the delivery of anti-fibrotic miR-223-3p and subsequent E2F1 suppression, which may suggest miR-223-3p-loaded ADSC-EVs to be a potential therapeutic approach for NAFLD.

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Cited by

Sorted by citations

Authors
Niu, Q., Wang, T., Wang, Z., Wang, F., Huang, D., Sun, H., & Liu, H.
Affiliations
Affiliated Hospital of Qingdao University (CN)
Corresponding author
Liu, Hanyun
Venue
Adipocyte
Published
2022-09-12
Volume
11
Issue
1
Pages
572-587
ISSN
  • 2162-3945 (ISSN-L)
  • 2162-397X
OpenAlex
W4295259903
Cited by
70
References
2
Citations by year
2026: 16 · 2025: 22 · 2024: 19 · 2023: 11 · 2022: 2
FWCI
4.41
Type
journal article
Language
en
Open access
Locations
  • Adipocyte (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
there is no funding associated
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
adipose-derived stem cells, extracellular vesicles, non-alcoholic fatty liver disease, miR-223-3p, E2F1, liver fibrosis, hepatic lipid accumulation, pyrrolizidine alkaloids, high-fat diet, cell-free therapy, microRNA delivery
MeSH terms
Extracellular Vesicles, Animals, Lipids, Liver Cirrhosis, MicroRNAs, Mice, Mesenchymal Stem Cells, Non-alcoholic Fatty Liver Disease

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