Cited by 109Circular RNAs in diseasesExtracellular vesicles in diseaseLiver physiology and pathology

Mesenchymal stem cell-originated exosomal circDIDO1 suppresses hepatic stellate cell activation by miR-141-3p/PTEN/AKT pathway in human liver fibrosis

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Ma, Li, Wei, Junfeng, Zeng, Yanli, Liu, Junping, Xiao, Erhui, Kang, Yuehua, Kang, Yi·2022·Drug Delivery

Abstract

, thus enabling personalized treatment. This study aimed to investigate the role of exosome-based delivery of circDIDO1 in liver fibrosis. Levels of genes and proteins were examined by qRT-PCR and Western blot. Cell proliferation, apoptosis, and cell cycle were analyzed by using cell counting kit-8 (CCK-8) assay, EdU assay, and flow cytometry, respectively. The binding between circDIDO1 and miR-141-3p was confirmed by dual-luciferase reporter, RNA pull-down and RIP assays. Exosomes were isolated by ultracentrifugation, and qualified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blot. CircDIDO1 overexpression or miR-141-3p inhibition suppressed the proliferation, reduced pro-fibrotic markers, and induced apoptosis as well as cell cycle arrest in hepatic stellate cells (HSCs) by blocking PTEN/AKT pathway. Mechanistically, circDIDO1 acted as an endogenous sponge for miR-141-3p, further rescue experiments showed that circDIDO1 suppressed HSC activation by targeting miR-141-3p. Extracellular circDIDO1 could be incorporated into exosomes isolated from mesenchymal stem cells (MSCs), and transmitted to HSCs to restrain HSC activation. Clinically, low levels of serum circDIDO1 in exosome were correlated with liver failure, and serum exosomal circDIDO1 had a well diagnostic value for liver fibrosis in liver failure patients. Transfer of circDIDO1 mediated by MSC-isolated exosomes suppressed HSC activation through the miR-141-3p/PTEN/AKT pathway, gaining a new insight into the prevention of liver fibrosis in liver failure patients.

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Crossref · 10.1080/10717544.2022.2030428

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Authors
Ma, L., Wei, J., Zeng, Y., Liu, J., Xiao, E., Kang, Y., & Kang, Y.
Affiliations
Zhengzhou University (CN)
Corresponding author
Kang, Yi
Venue
Drug Delivery
Published
2022-01-31
Volume
29
Issue
1
Pages
440-453
ISSN
  • 1071-7544 (ISSN-L)
  • 1521-0464
OpenAlex
W4210563368
Cited by
109
References
39
Citations by year
2026: 14 · 2025: 22 · 2024: 26 · 2023: 30 · 2022: 17
FWCI
7.76
Type
journal article
Language
en
Open access
Locations
  • Drug Delivery (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
liver fibrosis, hepatic stellate cell activation, mesenchymal stem cell-derived exosomes, miR-141-3p, PTEN/AKT pathway, microRNA sponge, exosome therapy, liver failure, serum biomarkers, cell cycle arrest
MeSH terms
RNA, Circular, Cell Line, DNA-Binding Proteins, Humans, Liver Cirrhosis, Signal Transduction, Apoptosis, MicroRNAs, Cell Proliferation, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Hepatic Stellate Cells, Exosomes, Mesenchymal Stem Cells

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