Bone Marrow Mesenchymal Stem Cell-Derived Exosomal miRNA-29c Decreases Cardiac Ischemia/Reperfusion Injury Through Inhibition of Excessive Autophagy via the PTEN/Akt/mTOR Signaling Pathway

Li, Te; Gu, Junlian; Ou, Yang; Wang, Jianmeng; Wang, Yonggang; Kong, Jing

doi:10.1253/circj.cj-19-1060

Cited by 52 publications

(31 citation statements)

References 50 publications

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“…A previous study showed that exosomes mainly exert their functions by transferring exosomal circRNAs or miRNAs to recipient cells. 34 In the current study, we found that IPAS-EXOs exerted their protective effects mainly via transfer of circSHOC2 to neurons, rather than by stimulating endogenous circSHOC2 expression within neurons. The effects of circSHOC2 were abolished via an autophagic inhibitor, suggesting that the neuroprotective role of circSHOC2 is mediated, at least in part, through autophagy.…”

Section: Discussionsupporting

confidence: 46%

Exosome-Shuttled circSHOC2 from IPASs Regulates Neuronal Autophagy and Ameliorates Ischemic Brain Injury via the miR-7670-3p/SIRT1 Axis

Chen

Wang

Zhu

et al. 2020

Molecular Therapy - Nucleic Acids

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The aim of the present study was to investigate the neuroprotective roles and mechanisms of the circular RNA circSHOC2 in ischemic-preconditioned astrocyte-derived exosomes (IPAS-EXOs) against ischemic stroke. We established an ischemia model based on oxygen glucose deprivation (OGD) in vitro and isolated resultant exosomes from astrocytes. Neuronal viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assays and TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling) staining, respectively. Autophagy-related proteins were analyzed by western blotting. We found that exosomes derived from IPAS-preconditioned medium (IPAS-CM) exerted neuroprotection. Furthermore, circSHOC2 expression was significantly upregulated in exosomes released from IPAS-CM. Overexpression of circSHOC2 in neurons yielded the same protective effects as those from IPAS-EXOs in vitro , and similar results were also observed in the middle cerebral artery occlusion (MCAO) mouse model. Mechanistically, circSHOC2 reduced neuronal apoptosis via regulating autophagy. Furthermore, circSHOC2 was found to sponge miR-7670-3p, which regulated SIRT1 expression. Transfection with an miR-7670-3p small interfering RNA (siRNA) (siRNA-7670-3p) and incubation with circSHOC2 extracellular vesicles attenuated ischemia-induced neuronal apoptosis in vivo and in vitro , while silencing of SIRT1 reversed the protective effects of exosomal circSHOC2 on hypoxic cerebral neurons. Taken together, our findings indicate that circSHOC2 in IPAS-EXOs suppressed neuronal apoptosis and ameliorated neuronal damage by regulating autophagy and acting on the miR-7670-3p/SIRT1 axis, which might contribute to a therapeutic strategy for ischemic stroke treatment.

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Section: Discussionsupporting

confidence: 46%

Exosome-Shuttled circSHOC2 from IPASs Regulates Neuronal Autophagy and Ameliorates Ischemic Brain Injury via the miR-7670-3p/SIRT1 Axis

Chen

Wang

Zhu

et al. 2020

Molecular Therapy - Nucleic Acids

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“…the I/R-induced excessive autophagy via the PTEN/AKT/mTOR signaling pathway (Li et al, 2020). Besides, through transfection, over expression of miR-301 in BMMSCs increases the expression of exosomal miR-301, which significantly reduces the ratio of LC3-II/LC3-I and increases P62 relative expression in the infarcted myocardial tissue.…”

Section: Exosomes Regulate Autophagy-dependent Cell Deathmentioning

confidence: 97%

“…In the mouse myocardial I/R injury model, the expression of miR-29c decreased, and the autophagy flow of myocardial cells increased. The high expression of miR-29c can reduce the excessive autophagy of hypoxic myocardium by directly inhibiting the expression of PTEN, thus inhibiting the I/R-induced excessive autophagy via the PTEN/AKT/mTOR signaling pathway ( Li et al, 2020 ). Besides, through transfection, over expression of miR-301 in BMMSCs increases the expression of exosomal miR-301, which significantly reduces the ratio of LC3-II/LC3-I and increases P62 relative expression in the infarcted myocardial tissue.…”

Section: Exosomes Reduce Cardiomyocyte Death After Myocardiac Injurymentioning

confidence: 99%

Cell Death and Exosomes Regulation After Myocardial Infarction and Ischemia-Reperfusion

Iroegbu

Peng³

et al. 2021

Front. Cell Dev. Biol.

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Cardiovascular disease (CVD) is the leading cause of death in the global population, accounting for about one-third of all deaths each year. Notably, with CVDs, myocardial damages result from myocardial infarction (MI) or cardiac arrhythmias caused by interrupted blood flow. Significantly, in the process of MI or myocardial ischemic-reperfusion (I/R) injury, both regulated and non-regulated cell death methods are involved. The critical factor for patients’ prognosis is the infarct area’s size, which determines the myocardial cells’ survival. Cell therapy for MI has been a research hotspot in recent years; however, exosomes secreted by cells have attracted much attention following shortcomings concerning immunogens. Exosomes are extracellular vesicles containing several biologically active substances such as lipids, nucleic acids, and proteins. New evidence suggests that exosomes play a crucial role in regulating cell death after MI as exosomes of various stem cells can participate in the cell damage process after MI. Hence, in the review herein, we focused on introducing various cell-derived exosomes to reduce cell death after MI by regulating the cell death pathway to understand myocardial repair mechanisms better and provide a reference for clinical treatment.

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“…After exosomes obtained from bone marrow mesenchymal stem cells (MSCs) included an elevated level of miR-29c were treated with H/R, their protective efficacy was distinctly decreased, which was associated with the level of exosomal miR-29c. Moreover, miR-29c could target the PTEN/AKT/mTOR signal pathway to reduce superabundant autophagy, thereby protecting heart from I/R injury [ 66 ].…”

Section: Ncrnas Regulate Autophagy In Myocardial I/r-injurymentioning

confidence: 99%

Non-coding RNAs modulate autophagy in myocardial ischemia-reperfusion injury: a systematic review

Huang

Mai

Chen

et al. 2021

J Cardiothorac Surg

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The myocardial infarction is the main cause of morbidity and mortality in cardiovascular diseases around the world. Although the timely and complete reperfusion via Percutaneous Coronary Intervention (PCI) or thrombolysis have distinctly decreased the mortality of myocardial infarction, reperfusion itself may lead to supererogatory irreversible myocardial injury and heart function disorders, namely ischemia-reperfusion (I/R) injury. Extensive studies have indicated that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play important roles in the progress of myocardial I/R injury, which is closely correlative with cardiomyocytes autophagy. Moreover, autophagy plays an important role in maintaining homeostasis and protecting cells in the myocardial ischemia reperfusion and cardiomyocyte hypoxia-reoxygenation (H/R) progress. In this review, we first introduced the biogenesis and functions of ncRNAs, and subsequently summarized the roles and relevant molecular mechanisms of ncRNAs regulating autophagy in myocardial I/R injury. We hope that this review in addition to develop a better understanding of the physiological and pathological roles of ncRNAs, can also lay a foundation for the therapies of myocardial I/R injury, and even for other related cardiovascular diseases.

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Bone Marrow Mesenchymal Stem Cell-Derived Exosomal miRNA-29c Decreases Cardiac Ischemia/Reperfusion Injury Through Inhibition of Excessive Autophagy via the PTEN/Akt/mTOR Signaling Pathway

Cited by 52 publications

References 50 publications

Exosome-Shuttled circSHOC2 from IPASs Regulates Neuronal Autophagy and Ameliorates Ischemic Brain Injury via the miR-7670-3p/SIRT1 Axis

Exosome-Shuttled circSHOC2 from IPASs Regulates Neuronal Autophagy and Ameliorates Ischemic Brain Injury via the miR-7670-3p/SIRT1 Axis

Cell Death and Exosomes Regulation After Myocardial Infarction and Ischemia-Reperfusion

Non-coding RNAs modulate autophagy in myocardial ischemia-reperfusion injury: a systematic review

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