Upregulated miR-206 Aggravates Deep Vein Thrombosis by Regulating GJA1-Mediated Autophagy of Endothelial Progenitor Cells

Li, Yan; Ge, Jingping; Yin, Yuanyuan; Yang, Ruowen; Kong, Jie; Gu, Jianping

doi:10.1155/2022/9966306

Cited by 11 publications

(10 citation statements)

References 43 publications

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“…In this study, we further noticed that GJA1 could markedly enhance ATP production rate and oxidative phosphorylation, meanwhile could protect the viability and the MMP of rat cardiomyocytes in HRI. It was reported that GJA1 maintained cellular connectivity and homeostasis by regulating autophagy [ 44 ]. Martins-Marques et al found that GJA1 was degraded in the setting of I/R, and it was correlated to autophagic activation [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

MiR-130a-3p regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial ischemia/reperfusion injury

et al. 2023

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Understanding the complex pathogenesis in myocardial ischemia/reperfusion (I/R) injury (IRI) is an urgent problem in clinical trials. Increasing pieces of evidence have suggested that miRNAs are involved in the occurrence and development of heart diseases by regulating mitochondria-related gene expression. Mitochondria have been acknowledged as the key triggers of cardiac I/R injury. However, the potential impact of miR-130a on mitochondria remains unclear in myocardial IRI. Exploring the regulatory mechanism of miR-130a on mitochondria may provide a new target for IRI therapy. In the present study, we found that miR-130a significantly increased in acute myocardial infarction (AMI) patients and myocardial I/R rats. MiR-130a could downregulate the viability of cardiomyocytes and the knockdown of miR-130a could protect the viability of cardiomyocytes under hypoxia-reoxygenation (HR). Over-expression of miR-130a resulted in mitochondrial dysfunction. It was evidenced by decreases in mitochondrial ATP production, mitochondrial membrane potential (MMP), and an increase in reactive oxygen species (ROS) production. However, suppression of miR-130a could protect against mitochondrial damage, show elevation of mitochondrial ATP production rate and MMP, and reduce ROS production. We further explored the effect of miR-130a on the mitochondrial quality control (QMC) system by determining mitochondrial-protein-specific proteases and analyzed mitochondrial morphology by fluorescence imaging and electron microscopy, respectively. It was noted that miR-130a could suppress mitochondrial fusion and FUNDC1-mediated mitophagy to accelerate myocardial IRI. Moreover, we investigated the potential miR-130a targeted mitochondria-related genes to understand the regulatory mechanism of miR-130a in the setting of myocardial IRI. It was revealed that miR-130a targeted GJA1, and GJA1 rescued IRI by enhancing ATP production rate and oxidative phosphorylation, meanwhile protecting cell viability, MMP, and activating mitophagy. In addition, the knockdown of miR-130a significantly activated FUNDC1-mediated mitophagy, while the knockdown of GJA1 reversed the relevant response. Collectively, our findings suggest that miR-130a regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial IRI.

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Section: Discussionmentioning

confidence: 99%

MiR-130a-3p regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial ischemia/reperfusion injury

et al. 2023

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“…In this study, we further noticed that GJA1 could markedly protect MMP of rat cardiomyocytes in HRI. It was reported that GJA1 maintained cellular connectivity and homeostasis by regulating autophagy (44). Martins-Marques et al found that GJA1 was degraded in the setting of I/R, and it was correlated to autophagic activation (26).…”

Section: Discussionmentioning

confidence: 99%

MiR-130a Regulates FUNDC1-Mediated Mitophagy by Targeting GJA1 in Myocardial Ischemia/Reperfusion Injury

Yan

Tian

Jia

et al. 2022

Preprint

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To understand the complex pathogenesis in myocardial ischemia/reperfusion (I/R) injury (IRI) is the urgent problem solved in clinical trials. Increasing evidences have suggested that miRNAs are involved in the occurrence and development of heart diseases by regulating the mitochondria-related genes expression. Mitochondria have been acknowledged as the key triggers of cardiac I/R injury. However, the potential impact of miR-130a on mitochondria remains unclear in myocardial IRI. Exploring the regulatory mechanism of miR-130a on mitochondria may provide a new target for IRI therapy. In the present study, we found that miR-130a was significantly increased in the acute myocardial infarction (AMI) patients and myocardial I/R rats. Over-expression of miR-130a resulted in mitochondrial dysfunction, evidenced by decreases in mitochondrial ATP production rate as well as mitochondrial membrane potential (MMP), and increase in reactive oxygen species (ROS) production. However, suppression of miR-130a could protect mitochondrial damage, showing elevation of mitochondrial ATP production rate and MMP, and reduction of ROS production. We further explored the effect of miR-130a on mitochondrial quality control (MQC) system by determining mitochondrial-protein-specific proteases, and mitochondrial morphology was analyzed by fluorescence imaging and electron microscopy, respectively. It was noted that miR-130a could obviously suppress mitochondrial fusion and FUNDC1-mediated mitophagy to accelerate myocardial IRI. Moreover, we investigated the potential miR-130a targetd mitochondria-related genes to understand the regulatory mechanism of miR-130a in the setting of myocardial IRI. It was revealed that miR-130a evidently targeted GJA1, and GJA1 rescued IRI through protecting MMP and activating mitophagy. In addition, knockdown of miR-130a significantly activated FUNDC1-mediated mitophagy, while knockdown of GJA1 reversed the relevant response. Collectively, our findings suggest that miR-130a regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial IRI.

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“…MicroRNAs (miRNAs) are the class of evolutionarily conserved noncoding RNAs with the function of regulating gene expression at the translational level 25,26 . MiRNAs were reported to play important roles in development of DVT, and lncRNAs were involved in regulation of DVT as competitive RNAs (ceRNAs) for miRNAs 13,22,27–29 . Study has shown that GUSBP5‐AS regulates angiogenesis and proliferation of EPCs through miR‐223‐3p, and alleviates development of DVT 30 .…”

Section: Introductionmentioning

confidence: 99%

“… 25 , 26 MiRNAs were reported to play important roles in development of DVT, and lncRNAs were involved in regulation of DVT as competitive RNAs (ceRNAs) for miRNAs. 13 , 22 , 27 , 28 , 29 Study has shown that GUSBP5‐AS regulates angiogenesis and proliferation of EPCs through miR‐223‐3p, and alleviates development of DVT. 30 In addition, downregulation of LINC01123 inhibited DVT formation via miRNA‐125a‐3p.…”

Section: Introductionmentioning

confidence: 99%

By modulating miR‐525‐5p/Bax axis, LINC00659 promotes vascular endothelial cell apoptosis

Zhu

Chen

2023

Immunity Inflam & Disease

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Background Deep vein thrombosis (DVT) is a vascular disease that has no effective treatment at present. Endothelial cells play a crucial role in the processes vasoconstriction, platelet activation, and blood coagulation and are an integral part of the vascular response to injury resulting in thrombus formation. Objective The aim of this study was to investigate the roles and mechanisms of long noncoding RNA LINC00659 (LINC00659) in endothelial cells. Methods The functions of LINC00659 and miR‐525‐5p on endothelial cells were explored by cell transfection assays, and the expression levels of LINC00659, miR‐525‐5p, and Bax in human umbilical vein endothelial cells (HUVECs) were assessed with reverse transcriptase‐quantitative polymerase chain reaction (RT‐qPCR). Binding sites of LINC00659 and miR‐525‐5p were subsequently analyzed with bioinformatics software, and validated with dual‐luciferase reporter gene assay. Effects of LINC00659 and miR‐525‐5p on proliferation and apoptosis of HUVECs were detected with MTT (3‐(45)‐dimethylthiahiazo (‐z‐y1)‐35‐di‐phenytetrazoliumromide) assay and flow cytometry. RT‐qPCR and western blot analysis were used to evaluate the mRNA and protein levels of apoptosis‐related markers Bcl‐2 and Bax in HUVECs. Results LINC00659 directly targeted and negatively regulated miR‐525‐5p, and Bax was a target of miR‐525‐5p. Upregulation of LINC00659 could inhibit proliferation and promote apoptosis of HUVECs, while the silencing of LINC00659 could increase the viability of HUVECs and inhibit apoptosis via upregulating miR‐525‐5p. Further mechanistic studies revealed miR‐525‐5p could negatively regulate Bax in HUVECs, and increased the viability of HUVECs and inhibited apoptosis by downregulating Bax expression. Conclusion LINC00659 played an important role in DVT by regulating the apoptosis of vascular endothelial cells through regulating miR‐525‐5p/Bax axis.

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Upregulated miR-206 Aggravates Deep Vein Thrombosis by Regulating GJA1-Mediated Autophagy of Endothelial Progenitor Cells

Cited by 11 publications

References 43 publications

MiR-130a-3p regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial ischemia/reperfusion injury

MiR-130a-3p regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial ischemia/reperfusion injury

MiR-130a Regulates FUNDC1-Mediated Mitophagy by Targeting GJA1 in Myocardial Ischemia/Reperfusion Injury

By modulating miR‐525‐5p/Bax axis, LINC00659 promotes vascular endothelial cell apoptosis

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