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Cited by 373Extracellular vesicles in diseaseMicroRNA in disease regulationMesenchymal stem cell research

Cardiac progenitor cell-derived exosomes prevent cardiomyocytes apoptosis through exosomal miR-21 by targeting PDCD4

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Xiao, J, Pan, Y, Li, X H, Yang, X Y, Feng, Y L, Tan, H H, Jiang, L, Feng, J +1 more·2016·Cell Death & Disease
DOI 10.1038/cddis.2016.181PMC PMC5143405
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Abstract

Cardiac progenitor cells derived from adult heart have emerged as one of the most promising stem cell types for cardiac protection and repair. Exosomes are known to mediate cell-cell communication by transporting cell-derived proteins and nucleic acids, including various microRNAs (miRNAs). Here we investigated the cardiac progenitor cell (CPC)-derived exosomal miRNAs on protecting myocardium under oxidative stress. Sca1(+)CPCs-derived exosomes were purified from conditional medium, and identified by nanoparticle trafficking analysis (NTA), transmission electron microscopy and western blotting using CD63, CD9 and Alix as markers. Exosomes production was measured by NTA, the result showed that oxidative stress-induced CPCs secrete more exosomes compared with normal condition. Although six apoptosis-related miRNAs could be detected in two different treatment-derived exosomes, only miR-21 was significantly upregulated in oxidative stress-induced exosomes compared with normal exosomes. The same oxidative stress could cause low miR-21 and high cleaved caspase-3 expression in H9C2 cardiac cells. But the cleaved caspase-3 was significantly decreased when miR-21 was overexpressed by transfecting miR-21 mimic. Furthermore, miR-21 mimic or inhibitor transfection and luciferase activity assay confirmed that programmed cell death 4 (PDCD4) was a target gene of miR-21, and miR-21/PDCD4 axis has an important role in anti-apoptotic effect of H9C2 cell. Western blotting and Annexin V/PI results demonstrated that exosomes pre-treated H9C2 exhibited increased miR-21 whereas decreased PDCD4, and had more resistant potential to the apoptosis induced by the oxidative stress, compared with non-treated cells. These findings revealed that CPC-derived exosomal miR-21 had an inhibiting role in the apoptosis pathway through downregulating PDCD4. Restored miR-21/PDCD4 pathway using CPC-derived exosomes could protect myocardial cells against oxidative stress-related apoptosis. Therefore, exosomes could be used as a new therapeutic vehicle for ischemic cardiac disease.

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  • The miR-21/PDCD4 pathway exerts anti-apoptotic effects against cell death in various diseases.

    “Existing evidence revealed that miR-21/PDCD4 pathway exerts anti-apoptotic effects against cell death in various diseases36.”

    From Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway (2017) · cites this paper as [36]

    The Results section reports that miR-21 reduced oxidative-stress-induced apoptosis in H9C2 cardiomyocytes by targeting PDCD4. The paper does not establish that this anti-apoptotic effect occurs across various diseases; its direct evidence is limited to the studied cardiac-cell model. Page numbers are not available in the supplied passages. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Xiao, J., Pan, Y., Li, X. H., Yang, X. Y., Feng, Y. L., Tan, H. H., Jiang, L., Feng, J., & Yu, X. Y.
Affiliations
Guangdong General Hospital (CN)
Corresponding author
Yu, X Y
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2016-06-23
Volume
7
Issue
6
Pages
e2277-e2277
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/cddis.2016.181
PMC
PMC5143405
OpenAlex
W2463234131
Cited by
373
References
5
Citations by year
2026: 17 · 2025: 26 · 2024: 28 · 2023: 29 · 2022: 40 · 2021: 55 · 2020: 62 · 2019: 48 · 2018: 40 · 2017: 24 · 2016: 4
FWCI
20.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81000835, 2015B020225006, #81120108003, 81330007)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
cardiac progenitor cells, exosomes, miR-21, PDCD4, cardiomyocyte apoptosis, oxidative stress, exosomal microRNAs, caspase-3, cardioprotection, ischemic heart disease, intercellular communication
MeSH terms
Animals, Humans, Hydrogen Peroxide, Male, Mice, Inbred C57BL, Models, Biological, Myocardium, Phenotype, Stem Cells, Apoptosis, Oxidative Stress, Cytoprotection, Myocytes, Cardiac, MicroRNAs, Cell Shape, Apoptosis Regulatory Proteins, Rats, Exosomes, HEK293 Cells

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