The BMSC-derived exosomal lncRNA Mir9-3hg suppresses cardiomyocyte ferroptosis in ischemia-reperfusion mice via the Pum2/PRDX6 axis

Zhang, Jiankai; Zhang, Zhi; Guo, Zi-ao; Fu, Yunqi; Chen, Xiao‐Jia; Chen, Weijie; Wu, Hao; Cui, Xiaojun

doi:10.1016/j.numecd.2021.10.017

Cited by 53 publications

(37 citation statements)

References 23 publications

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“…In the setting of myocardial IR injury, one study demonstrated that MSC-derived exosomes inhibited cardiomyocytes pyroptosis through the regulation of miRNA-100-5p/forkhead box O3/NLRP3 signaling pathway after hypoxia/reoxygenation injury ( Liang et al, 2021 ). Another two studies demonstrated that MSC-derived exosomes attenuated myocardial injury by inhibiting cardiac ferroptosis through promoting miR-23a-3p-mediated suppression of divalent metal transporter 1 expression and modulating the pumilio RNA binding family member 2/peroxiredoxin 6 axis, respectively ( Song et al, 2021 ; Zhang et al, 2021 ). In the setting of cerebral IR injury, one study demonstrated that MSC-derived exosomes decreased microglial pyroptosis by enhancing forkhead box O3a-mediated mitophagy and subsequently alleviated neuronal injury under hypoxia/reoxygenation ( Hu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Alleviate Post-resuscitation Cardiac and Cerebral Injuries by Inhibiting Cell Pyroptosis and Ferroptosis in a Swine Model of Cardiac Arrest

Zhang

Liu

et al. 2021

Front. Pharmacol.

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Following cardiopulmonary resuscitation (CPR), the ensuing cardiac and cerebral injuries contribute to the poor outcome of cardiac arrest (CA) victims, in which the pathogenetic process is possibly driven by cell pyroptosis and ferroptosis. Mesenchymal stem cells (MSCs) have been shown to be a promising strategy for post-resuscitation cardiac and cerebral protection in rat, but its effectiveness in the clinically relevant swine model and the potential protective mechanism remain unknown. The present study was designed to investigate whether MSCs administration could alleviate post-resuscitation cardiac and cerebral injuries through the inhibition of cell pyroptosis and ferroptosis in swine. Twenty-four male domestic swine were randomly divided into three groups: sham, CPR, and MSC. A dose of 2.5×106/kg of MSCs derived from human embryonic stem cells was intravenously infused at 1.5, and 3 days prior to CA. The animal model was established by 8 min of CA and then 8 min of CPR. After resuscitation, cardiac, cerebral function and injury biomarkers were regularly evaluated for a total of 24 h. At 24 h post-resuscitation, pyroptosis-related proteins (NLRP3, ASC, cleaved caspase-1, GSDMD), proinflammatory cytokines (IL-1β, IL-18), ferroptosis-related proteins (ACSL4, GPX4) and iron deposition in the heart, cortex and hippocampus were measured. Consequently, significantly greater cardiac, cerebral dysfunction and injuries after resuscitation were observed in the CPR and MSC groups compared with the sham group. However, the severity of cardiac and cerebral damage were significantly milder in the MSC group than in the CPR group. In addition, the expression levels of NLRP3, ASC, cleaved caspase-1, GSDMD and ACSL4, the contents of IL-1β and IL-18, and the level of iron deposition were significantly higher while the expression level of GPX4 was significantly lower in the heart, cortex and hippocampus in all resuscitated animals compared with the sham group. Nevertheless, MSCs administration significantly decreased post-resuscitation cardiac, cerebral pyroptosis and ferroptosis compared to the CPR group. Our results showed that the administration of MSCs significantly alleviated post-resuscitation cardiac and cerebral injuries in swine, in which the protective effects were related to the inhibition of cell pyroptosis and ferroptosis.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Alleviate Post-resuscitation Cardiac and Cerebral Injuries by Inhibiting Cell Pyroptosis and Ferroptosis in a Swine Model of Cardiac Arrest

Zhang

Liu

et al. 2021

Front. Pharmacol.

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“…Likewise, Xanthohumol (XN) isolated from Humulus lupulus had also been shown to protect ischemic/reperfusion myocardium from ferroptosis ( 57 ). Besides, exosomal long noncoding RNA (lncRNA) MIR9-3 host gene (Mir9-3hg) derived from bone MSCs mitigated ferroptosis in I/RI mice by regulating pumilio RNA binding family member two (Pum2)/peroxiredoxin 6 (PRDX6) axis and showed cardioprotective effects both in vitro and in vivo ( 58 ). These exciting findings have further broadened therapeutic approaches for ferroptosis in I/RI.…”

Section: Ferroptosis and Cardiovascular Diseasesmentioning

confidence: 99%

Roles of Ferroptosis in Cardiovascular Diseases

Guo

Zhang

Zhou

et al. 2022

Front. Cardiovasc. Med.

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Ferroptosis is an iron-dependent regulated cell death characterized by lipid peroxidation and iron overload, which is different from other types of programmed cell death, including apoptosis, necroptosis, autophagy, and pyroptosis. Over the past years, emerging studies have shown a close relation between ferroptosis and various cardiovascular diseases such as atherosclerosis, acute myocardial infarction, ischemia/reperfusion injury, cardiomyopathy, and heart failure. Herein, we will review the contributions of ferroptosis to multiple cardiovascular diseases and the related targets. Further, we discuss the potential ferroptosis-targeting strategies for treating different cardiovascular diseases.

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“…In murine cardiomyocytes, Mir9-3hg, an exosomal long non-coding RNA derived from bone marrow stem cells, inhibited I/R-induced ferroptosis by directly targeting the Pumilio 2 (PUM2)/PRDX6 axis. Incubation with BMSC-Exos enhanced GSH levels and diminished Fe 2+ concentration, ROS, and ferroptosis biomarker expression in H/R-treated cells, whereas these effects can be reversed by intervention with Mir9-3hg [ 72 ].…”

Section: Mechanisms and Targeted Therapies For Ferroptosis In Irimentioning

confidence: 99%

Ferroptosis—A New Dawn in the Treatment of Organ Ischemia–Reperfusion Injury

Zhou

Han

Guo

et al. 2022

Cells

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Ischemia–reperfusion (I/R) is a common pathological phenomenon that occurs in numerous organs and diseases. It generally results from secondary damage caused by the recovery of blood flow and reoxygenation, followed by ischemia of organ tissues, which is often accompanied by severe cellular damage and death. Currently, effective treatments for I/R injury (IRI) are limited. Ferroptosis, a new type of regulated cell death (RCD), is characterized by iron overload and iron-dependent lipid peroxidation. Mounting evidence has indicated a close relationship between ferroptosis and IRI. Ferroptosis plays a significantly detrimental role in the progression of IRI, and targeting ferroptosis may be a promising approach for treatment of IRI. Considering the substantial progress made in the study of ferroptosis in IRI, in this review, we summarize the pathological mechanisms and therapeutic targets of ferroptosis in IRI.

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The BMSC-derived exosomal lncRNA Mir9-3hg suppresses cardiomyocyte ferroptosis in ischemia-reperfusion mice via the Pum2/PRDX6 axis

Cited by 53 publications

References 23 publications

Mesenchymal Stem Cells Alleviate Post-resuscitation Cardiac and Cerebral Injuries by Inhibiting Cell Pyroptosis and Ferroptosis in a Swine Model of Cardiac Arrest

Mesenchymal Stem Cells Alleviate Post-resuscitation Cardiac and Cerebral Injuries by Inhibiting Cell Pyroptosis and Ferroptosis in a Swine Model of Cardiac Arrest

Roles of Ferroptosis in Cardiovascular Diseases

Ferroptosis—A New Dawn in the Treatment of Organ Ischemia–Reperfusion Injury

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