Bone marrow mesenchymal stem cell-secreted exosomes carrying microRNA-125b protect against myocardial ischemia reperfusion injury via targeting SIRT7
Open accessAbstract
MicroRNA-125b (miR-125b) reduces myocardial infarct area and restrains myocardial ischemia reperfusion injury (I/R). In this study, we aimed to investigate the effect of bone marrow mesenchymal stem cell (BMSC)-derived exosomes carrying miR-125b on I/R rats. The myocardial I/R model in rats was constructed by ligation of the left anterior descending coronary artery (LAD). Rats were randomly divided into I/R and Sham group. Lv-cel-miR-67 (control) or Lv-miR-125b was transfected into BMSCs. Exosomes were extracted from transfected BMSCs, and separately named BMSC-Exo-67, BMSC-Exo-125b, and BMSC-Exo. MTT assay and flow cytometry were used to detect the viability and apoptosis of I/R myocardium cells, respectively. The expression of cell apoptosis proteins and the levels of inflammatory factors were examined by Western blot and ELISA assay, respectively. The target relationship between miR-125b and SIRT7 was predicted by using StarBase3.0, and was confirmed by using dual-luciferase reporter gene assay. qRT-PCR, immunohistochemistry staining, and Western blot were used to evaluate the expression of SIRT7 in myocardium tissues in I/R rats. BMSC-derived exosomes were successfully isolated and identified by TEM and positive expression of CD9 and CD63. The expression of miR-125b was down-regulated in I/R myocardium tissues and cells. BMSC-Exo-125b significantly up-regulated miR-125b in I/R myocardium cells. The intervention of BMSC-Exo-125b significantly increased the cell viability, decreased the apoptotic ratio, down-regulated Bax and caspase-3, up-regulated Bcl-2, and decreased the levels of IL-1β, IL-6, and TNF-α in I/R myocardium cells. SIRT7 was a target of miR-125b, and BMSC-Exo-125b significantly down-regulated SIRT7 in myocardium cells. In addition, the injection of BMSC-Exo-125b alleviated the pathological damages and down-regulated SIRT7 in myocardium tissues of I/R rats. BMSC-derived exosomes carrying miR-125b protected against myocardial I/R by targeting SIRT7.
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Bone marrow-secreted MSC exosomes carrying miRNA-125b could prevent myocardial ischemia-reperfusion injury by targeting SIRT7.
“Similarly, Chen et al. showed that bone marrow-secreted MSC exosomes carrying miRNA-125b could prevent myocardial ischemia-reperfusion injury by targeting SIRT7 [93].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [93]
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- Authors
- Chen, Q., Liu, Y., Ding, X., Li, Q., Qiu, F., Wang, M., Shen, Z., Zheng, H., & Fu, G.
- Affiliations
- Sir Run Run Shaw Hospital (CN)
- Nanjing Drum Tower Hospital (CN)
- Zhejiang Provincial People's Hospital (CN)
- Corresponding author
- Zheng, Hao
- Fu, Guosheng
- Venue
- Molecular and Cellular Biochemistry
- Published
- 2019-12-19
- Volume
- 465
- Issue
- 1-2
- Pages
- 103-114
- ISSN
- 0300-8177 (ISSN-L)
- 1573-4919
- PMC
- PMC6955239
- OpenAlex
- W2996170603
- Cited by
- 146
- References
- 47
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 24 · 2023: 26 · 2022: 30 · 2021: 26 · 2020: 9
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular and Cellular Biochemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Effects and mechanisms of microRNA and O-GlcNAcylation on paracrine function of diabetic endothelial progenitor cell (Y18H020004)
- The mechanism research identifing Oct4 upregulating Cripto-1 mediated osteoblast differentiation of valve interstitial cells during the pathogenesis of aortic valve calcification (81800342)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- bone marrow mesenchymal stem cells, exosomes, miR-125b, SIRT7, myocardial ischemia-reperfusion injury, cardioprotection, apoptosis, inflammation, stem cell-derived exosomes, myocardial infarction, Bax, caspase-3, Bcl-2, inflammatory cytokines, microRNA target regulation, exosome delivery
- MeSH terms
- Animals, Bone Marrow Cells, Male, Myocardial Reperfusion Injury, Cytokines, Rats, Sprague-Dawley, Apoptosis, MicroRNAs, Sirtuins, Rats, Exosomes, Mesenchymal Stem Cells
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