Mesenchymal stem cells-derived exosomes prevent sepsis-induced myocardial injury by a CircRTN4/miR-497-5p/MG53 pathway

Jiang, Li; Jiang, Rui; Hou, Yuanyuan; Lin, Aiqin

doi:10.1016/j.bbrc.2022.05.094

Cited by 26 publications

(15 citation statements)

References 36 publications

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“…The present results for PKH26-labeled exosomes demonstrated that exosomes from HUVECs were mainly located in the cytoplasm of VSMCs. Similarly, Li et al (36) also reported that exosomal circRTN4 from mesenchymal stem cells could alleviate sepsis-induced myocardial injury, and their fluorescence in situ hybridization assay results demonstrated the location of circRTN4 in the cytoplasm of cardiomyocytes. Although the details of exosome localization in the cytoplasm need to be further explored, the present study revealed that exosomes could serve as an important cargo transporter between HUVECs and VSMCs and are thus involved in the process of VC.…”

Section: Discussionmentioning

confidence: 84%

Exosomal STAT1 derived from high phosphorus‑stimulated vascular endothelial cells induces vascular smooth muscle cell calcification via the Wnt/β‑catenin signaling pathway

Zheng

et al. 2022

Int J Mol Med

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Vascular calcification is commonly observed in chronic kidney disease. The mechanism of how the calcification signal from endothelial cells is transmitted to vascular smooth muscle cells (VSMCs) remains unknown. The aim of the present study was to investigate whether exosomes from HUVECs (HUVEC-Exos) could regulate VSMC calcification and its potential signaling pathway. HUVEC-Exos were isolated from HUVECs under no phosphorus (NP) and high phosphorus (HP) conditions. Alizarin Red S staining and calcium (Ca) content analysis were carried out to detect calcification in VSMCs. Proteomics analysis was carried out to detect the differential expression of exosomal proteins. Protein and mRNA levels were measured by western blot analysis and reverse transcription-quantitative PCR (RT-qPCR). Exosomes derived from HP-HUVECs promoted the calcification of VSMCs, as assessed by Alizarin Red S staining, alkaline phosphatase activity assays, Ca content measurements and the increased expression of runt-related transcription factor 2 and osteopontin. Proteomic analysis detected the upregulation of STAT1 in HP-exosomes from HUVECs (HUVEC-Exos) compared with NP-HUVEC-Exos, which was also confirmed by western blot analysis and RT-qPCR. Inhibition of STAT1 expression in VSMCs using fludarabine or knockdown of STAT1 expression using small interfering RNA alleviated the calcification of VSMCs. Furthermore, lithium chloride (Wnt activator) reversed the protective effect of STAT1 inhibition on VSMC calcification, while Dickkopf-1 (Wnt inhibitor) exerted the opposite effect, suggesting that activation of the Wnt/β-catenin signaling pathway was involved in STAT1-mediated VSMC calcification. In conclusion, the present results indicated that exosomal STAT1 derived from HP-treated HUVECs could promote VSMC calcification, and activation of the Wnt/β-catenin pathway may be a potential mechanism of the VSMC calcification promoted by exosomes.

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Section: Discussionmentioning

confidence: 84%

Exosomal STAT1 derived from high phosphorus‑stimulated vascular endothelial cells induces vascular smooth muscle cell calcification via the Wnt/β‑catenin signaling pathway

Zheng

et al. 2022

Int J Mol Med

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“…In this setting, data suggest that effects are, at least in part, mediated by delivering the circular RNA circRTN4 to cardiomyocytes. circRTN4 effectively relieves cardiac injury and apoptosis, suppresses oxidative stress, and reduces inflammatory markers in sepsis-induced rats and lipopolysaccharide (LPS)-treated cardiomyocytes through its regulatory role in the miR-497-5p/MG53 pathway, where circRTN4 acts on miR-497-5p to upregulate MG53 which subsequently repairs damaged cell membranes [ 135 , 136 ]. The role of microRNA as key mediators of the beneficial effects of stem cell-derived EVs is further supported by the findings that cardiac progenitor cell (CPC)-derived exosomes expressing GATA4-responsive-miR-451 effectively protect cardiomyoblasts from ischemia/reperfusion injury-mediated oxidative stress suppressing caspase 3/7 activation.…”

Section: Role Of Stem Cell-derived Extracellular Vesicles In Heart Di...mentioning

confidence: 99%

Stem Cell-Derived Extracellular Vesicles in the Treatment of Cardiovascular Diseases

McDonald,

Mohak,

Fabian

2024

Pharmaceutics

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Cardiovascular disease constitutes a noteworthy public health challenge characterized by a pronounced incidence, frequency, and mortality rate, particularly impacting specific demographic groups, and imposing a substantial burden on the healthcare infrastructure. Certain risk factors, such as age, gender, and smoking, contribute to the prevalence of fatal cardiovascular disease, highlighting the need for targeted interventions. Current challenges in clinical practice involve medication complexities, the lack of a systematic decision-making approach, and prevalent drug therapy problems. Stem cell-derived extracellular vesicles stand as versatile entities with a unique molecular fingerprint, holding significant therapeutic potential across a spectrum of applications, particularly in the realm of cardio-protection. Their lipid, protein, and nucleic acid compositions, coupled with their multifaceted functions, underscore their role as promising mediators in regenerative medicine and pave the way for further exploration of their intricate contributions to cellular physiology and pathology. Here, we overview our current understanding of the possible role of stem cell-derived extracellular vesicles in the clinical management of human cardiovascular pathologies.

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“…Circular RNA is another emerging class of noncoding RNAs. Although not well studied, they are located in specific subcellular compartments and have been implicated in cardiac repair [ 51 , 52 ].…”

Section: Msc-derived Exosomes and Noncoding Rnasmentioning

confidence: 99%

“…The cytoplasmic circRNA CircRTN4 was found to alleviate cardiac injury, apoptosis, and oxidative stress in a rat model of sepsis-induced myocardial injury. Further, it was observed that circRTN4 interacted with miR-497-5p to upregulate MG53 expression in cardiomyocytes, thereby mitigating cardiomyocyte damage [ 51 ]. In another study, circ-0001273 delivered by human umbilical cord MSC-derived exosomes inhibited myocardial cell apoptosis in ischemic conditions, promoting MI repair [ 52 ].…”

Section: The Role Of Msc-derived Lncrnas In Cardiac Injury and Repairmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Long Noncoding RNAs in Cardiac Injury and Repair

Tran,

Cruz,

Chan

et al. 2023

Cells

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Cardiac injury, such as myocardial infarction and heart failure, remains a significant global health burden. The limited regenerative capacity of the adult heart poses a challenge for restoring its function after injury. Mesenchymal stem cells (MSCs) have emerged as promising candidates for cardiac regeneration due to their ability to differentiate into various cell types and secrete bioactive molecules. In recent years, attention has been given to noncoding RNAs derived from MSCs, particularly long noncoding RNAs (lncRNAs), and their potential role in cardiac injury and repair. LncRNAs are RNA molecules that do not encode proteins but play critical roles in gene regulation and cellular responses including cardiac repair and regeneration. This review focused on MSC-derived lncRNAs and their implications in cardiac regeneration, including their effects on cardiac function, myocardial remodeling, cardiomyocyte injury, and angiogenesis. Understanding the molecular mechanisms of MSC-derived lncRNAs in cardiac injury and repair may contribute to the development of novel therapeutic strategies for treating cardiovascular diseases. However, further research is needed to fully elucidate the potential of MSC-derived lncRNAs and address the challenges in this field.

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Mesenchymal stem cells-derived exosomes prevent sepsis-induced myocardial injury by a CircRTN4/miR-497-5p/MG53 pathway

Cited by 26 publications

References 36 publications

Exosomal STAT1 derived from high phosphorus‑stimulated vascular endothelial cells induces vascular smooth muscle cell calcification via the Wnt/β‑catenin signaling pathway

Exosomal STAT1 derived from high phosphorus‑stimulated vascular endothelial cells induces vascular smooth muscle cell calcification via the Wnt/β‑catenin signaling pathway

Stem Cell-Derived Extracellular Vesicles in the Treatment of Cardiovascular Diseases

Mesenchymal Stem Cell-Derived Long Noncoding RNAs in Cardiac Injury and Repair

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