ArticleStem cell research & therapy2020
Overexpression of GATA4 enhances the antiapoptotic effect of exosomes secreted from cardiac colony-forming unit fibroblasts via miRNA221-mediated targeting of the PTEN/PI3K/AKT signaling pathway.
Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Small Extracellular Vesicles in Cardioprotection, Cardiac Repair, and Regeneration: Cargo Mechanisms, Producer Cell Sources, and Translational Development.Biomedicines · 2026Review
- Dysregulation of miRNAs in Sicilian Patients with Autism Spectrum Disorder.Biomedicines · 2026Article
- Mechanisms and emerging research trends of angiogenesis promotion by small extracellular vesicles from different cellular sources in alleviating myocardial infarction injury.Frontiers in pharmacology · 2026Review
- Organ-Specific Extracellular Vesicles in the Treatment of Ischemic Acute Organ Injury: Mechanisms, Successes, and Prospects.International journal of molecular sciences · 2025Review
- Inhibition of ceramide synthesis improves the outcome of ischemia/reperfusion injury in cardiomyocytes derived from human induced pluripotent stem cell.Stem cell research & therapy · 2025Article
- MicroRNA-specific therapeutic targets and biomarkers of apoptosis following myocardial ischemia-reperfusion injury.Molecular and cellular biochemistry · 2024Review
- Review
- TIM proteins and microRNAs: distinct impact and promising interactions on transplantation immunity.Frontiers in immunology · 2024Review
- Regulation mechanism of microRNAs in cardiac cells-derived exosomes in cell crosstalk.Frontiers in pharmacology · 2024Review
- Mechanisms and therapeutic strategies of extracellular vesicles in cardiovascular diseases.MedComm · 2023Review
- Article
- Exosomes as a Cell-free Therapy for Myocardial Injury Following Acute Myocardial Infarction or Ischemic Reperfusion.Aging and disease · 2022Review
- Overexpression of GATA binding protein 4 and myocyte enhancer factor 2C induces differentiation of mesenchymal stem cells into cardiac-like cells.World journal of stem cells · 2022Article
- Tripartite motif 38 attenuates cardiac fibrosis after myocardial infarction by suppressing TAK1 activation via TAB2/3 degradation.iScience · 2022Article
- Extracellular vesicles in cardiovascular disease: Biological functions and therapeutic implications.Pharmacology & therapeutics · 2022Review
- Extracellular Vesicles in Cardiovascular Diseases: Diagnosis and Therapy.Frontiers in cell and developmental biology · 2022Review
- The Networks of Noncoding RNAs and Their Direct Molecular Targets in Myocardial Infarction.International journal of biological sciences · 2022Review
- Identifying the Predictive Role of Oxidative Stress Genes in the Prognosis of Glioma Patients.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Article
- Therapeutic and diagnostic targeting of fibrosis in metabolic, proliferative and viral disorders.Advanced drug delivery reviews · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGATA4 is an early cardiac-specific transcription factor, and endogenous GATA4-positive cells play a critical role in cardioprotection after myocardial injury. As functional paracrine units of therapeutic cells, exosomes can partially reproduce the reparative properties of their parental cells. Here, we investigated the cardioprotective capabilities of exosomes derived from cardiac colony-forming unit fibroblasts (cCFU-Fs) overexpressing GATA4 (cCFU-Fs
methodsExosomes were harvested from cCFU-Fs by ultracentrifugation. miRNA arrays were performed to determine differential miRNA expression between exosomes derived from cCFU-Fs
resultsCompared with NC-Exo, GATA4-Exo increased the survival and reduced the apoptosis of H9c2 cells. Direct intramyocardial transplantation of GATA4-Exo at the border of the ischemic region following ligation of the left anterior descending (LAD) coronary artery significantly restored cardiac contractile function and reduced infarct size. Microarray analysis revealed significantly increased miR221 expression in GATA4-Exo. qPCR confirmed higher miR221 levels in H9c2 cells treated with GATA4-Exo than in those treated with NC-Exo. miR221 mimic-transfected H9c2 cells demonstrated a significantly higher survival rate following exposure to hypoxic conditions than those transfected with miR221 inhibitor. A dual-luciferase reporter gene assay confirmed the PTEN gene as a target of miR221. Western blot analysis showed that H9c2 cells treated with GATA4-Exo exhibited lower PTEN protein expression and higher p-Akt expression.
conclusionGATA4 overexpression enhances the protective effect of cCFU-F-derived exosomes on myocardial ischemic injury. In terms of the mechanism, it is at least partly due to the miR221 transferred by GATA4-Exo, which inhibits PTEN expression, activates the phosphatidylinositol 3 kinase (PI3K)/AKT signaling pathway, and subsequently alleviates apoptosis of myocardial cells (CMs).
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