Impact of miR-208 and its Target Gene Nemo-Like Kinase on the Protective Effect of Ginsenoside Rb1 in Hypoxia/Ischemia Injuried Cardiomyocytes

Yan, Xu; Liu, Jianxun; Wu, Hongjin; Liu, Yuna; Zheng, Sidao; Zhang, Chengying

doi:10.1159/000447825

Cited by 39 publications

(26 citation statements)

References 35 publications

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“…Although it is unlikely that a single biomarker of myocardial ischemic injury will be sufficient to manage AMI diagnosis, a combination of different biomarkers, including circulating miRNAs, may enhance diagnostic sensitivity and specificity [28]. Numerous circulating miRNAs, including miR-208a, miR-126, miR-223-3p, miR-150, miR-19b-3p, miR-21, miR-328, and miR-134, showed potential as biomarkers for cardiovascular diseases [28][29][30][31][32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Circulating miR-181a as a Potential Novel Biomarker for Diagnosis of Acute Myocardial Infarction

Zhu

Yao

Wang

et al. 2016

Cell Physiol Biochem

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Background: In this study, we tested the hypothesis that miR-181a levels increase during acute myocardial infarction. We investigated circulating miR-181a as a potential novel biomarker for early diagnosis of acute myocardial infarction (AMI). Methods: From June 2014 to June 2016, 120 consecutive eligible patients with AMI (n = 60) or unstable angina (UA; n = 60) and 60 control subjects were enrolled. Plasma miR-181a levels were determined by quantitative reverse transcriptase-polymerase chain reaction. Results: Circulating miR-181a expression levels detected immediately after admission were higher in the AMI group than in the UA and control groups. Relative miR-181a levels in AMI patients were positively correlated with the concentrations of the creatine kinase-MB fraction and cardiac troponin I. Correlation analysis showed that plasma miR-181a was positively correlated with coronary Gensini score (r = 0.573, P < 0.05) and negatively correlated with left ventricular ejection fraction (r = -0.489, P < 0.05). Receiver operating characteristic curve analyses showed that plasma miR-181a was of significant diagnostic value for AMI (AUC, 0.834; 95% CI, 0.756-0.912, P < 0.05). Conclusion: Circulating miR-181a levels in patients with AMI were significantly changed in a time-dependent manner, indicating the value of plasma miR-181a as a novel biomarker for diagnosing AMI.

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Section: Discussionmentioning

confidence: 99%

Circulating miR-181a as a Potential Novel Biomarker for Diagnosis of Acute Myocardial Infarction

Zhu

Yao

Wang

et al. 2016

Cell Physiol Biochem

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“…Based on these results, miR-3546 was selected to further determine its effect on sublytic C5b-9-triggered GMC apoptosis and the related regulatory mechanism. Notably, miR-3546 belongs to miR-208 family, and though several documents have pointed out that miR-208 has regulatory role in myocardial injury [42][43][44], there has not been any report about the function of miR-3546.…”

Section: Discussionmentioning

confidence: 99%

Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis Through miR-3546/SOX4/Survivin Axis in Rat Thy-1 Nephritis

Yao

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: The activation of complement system and the formation of C5b-9 complex have been confirmed in the glomeruli of patients with mesangioproliferative glomerulonephritis (MsPGN). However, the role and mechanism of C5b-9-induced injury in glomerular mesangial cell (GMC) are poorly understood. Rat Thy-1N is an animal model for studying MsPGN. It has been revealed that the attack of C5b-9 to the GMC in rat Thy-1N is sublytic, and sublytic C5b-9 can cause GMC apoptosis, but the underlying mechanism is not fully elucidated. To explore the role and regulatory mechanism of C5b-9 in MsPGN lesion, we used rat Thy-1N model and first detected the change of microRNA (miRNA) profiles both in Thy-1N rat renal tissues (in vivo) and in the cultured GMCs with sublytic C5b-9 stimulation (in vitro). Then we determined the effect of miR-3546, which increased both in vivo and in vitro, on GMC apoptosis upon sublytic C5b-9 as well as the involved mechanism. Methods: Rat Thy-1N model was established and GMCs were treated with sublytic C5b-9. The rat renal cortex and the stimulated GMCs were obtained for miRNA microarray detection. Subsequently, the increased miRNAs were verified by real-time PCR. Meanwhile, to ascertain the ability of some miRNAs to upregulate cleaved caspase 3 and induce GMC apoptosis, the corresponding miRNA mimics were transfected into GMCs, followed by western blotting (WB) and flow cytometry mesurement. Thereafter, the miR-3546-targeted gene (SOX4) was predicted using bioinformatics approaches, and SOX4 expression in Thy-1N tissues and in the GMCs upon sublytic C5b-9 stimulation or miR-3546 mimic/inhibitor transfection were detected using real-time PCR and WB. To prove that miR-3546 can affect SOX4 gene transcription and SOX4 can regulate survivin expression, dual luciferase reporter assay, real-time PCR, WB and chromatin immunoprecipitation (ChIP) assays were performed. Furthermore, the role of miR-3546/SOX4/survivin axis in the GMC apoptosis induced by sublytic C5b-9 was examined using WB and flow cytometry. Results: Compared with normal renal tissues and untreated GMCs, there were 43 and 62 upregulated miRNAs (> 2-fold) in Thy-1N tissues and sublytic C5b-9-stimulated GMCs respectively. A total of 17 miRNAs were increased both in vivo and in vitro, 11 of which were validated by real-time PCR. Among them, miR-3546 could markedly promote GMC apoptosis and inhibit SOX4 or survivin expression in response to sublytic C5b-9, and either SOX4 or survivin overexpression markedly rescued the GMC apoptosis mediated by miR-3546 mimic. Additionally, SOX4 overexpression could reverse the survivin suppression by miR-3546 mimic, and SOX4 could bind to survivin promoter (-1,278 to -853 nt) and activate survivin gene transcription. Conclusion: MiR-3546/ SOX4/survivin axis has a promoting role in the GMC apoptosis triggered by sublytic C5b-9, and our findings may provide a new insight into the pathogenesis of rat Thy-1N and human MsPGN.

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“…Culture of neonatal rat cardiomyocytes (NRCMs) from heart tissues. Primary cultures of NRCMs from a total of 180 12-24 h-old male Sprague Dawley rats (weight range, 5-6 g; Laboratory Animal Center, Jilin University, Changchun, China) were prepared through gentle serial trypsinization, as described previously (12)(13)(14). All animal protocols were approved by the Animal Care Center and Use Committee of Jilin University (Changchun, China).…”

Section: Methodsmentioning

confidence: 99%

“…Ginsenoside Rb1 (GS-Rb1) is the most active and abundant monomer in ginseng (11). Although a number of studies have demonstrated the protective effects of GS-Rb1 on the heart (11)(12)(13)(14) and recent studies have revealed that GS-Rb1 could impact miR expression in hypoxia/ischemia-injured cardiomyocytes (12,13), the miR targets involved and their roles in the heart remain unknown. Therefore, in the current study, the roles and mechanisms of miR-21 and its target gene, which encodes PDCD4, in the protection of cardiomyocytes treated with GS-Rb1 were studied by constructing an oxygen-glucose deprivation (OGD) injury model in vitro.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rb1 protects cardiomyocytes from oxygen‑glucose deprivation injuries by targeting microRNA‑21

Yang

Liu

et al. 2019

Exp Ther Med

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Ginsenoside Rb1 (GS-Rb1) is one of the most important active pharmacological extracts of the traditional Chinese medicine, ginseng, and there is extensive evidence of its cardioprotective properties. However, the microRNA (miR) targets of GS-Rb1 and the underlying mechanisms of GS-Rb1 and miR-21 in the progression of cardiomyocyte apoptosis have not been clearly elucidated. The aim of the current study was to investigate the impact of miR-21 and its target gene, programmed cell death protein 4 (PDCD4), on the protective effect of GS-Rb1 in cardiomyocytes injured by oxygen-glucose deprivation (OGD). The miR-21 expression levels were downregulated, and the percentage of the apoptotic cells and reactive oxygen species (ROS) was increased in OGD-cultured neonatal rat cardiomyocytes; however, the effects were reversed by GS-Rb1 treatment. It was demonstrated that GS-Rb1 could reduce intracellular ROS content, and the expression of cytochrome C and the pro-apoptosis protein, apoptosis regulator B-cell lymphoma associated X (Bax) protein while increasing the expression of the anti-apoptosis protein, apoptosis regulator Bcl-2. The target gene, PDCD4, was significantly upregulated in the OGD group; however, the expression of PDCD4 was inhibited by GS-Rb1 treatment. Furthermore, miR-21 inhibitor transfection reduced GS-Rb1-induced miR-21 upregulation compared with the OGD+GS-Rb1 group, indicating that the miR-21 was involved in the anti-apoptotic effect of GS-Rb1 in cardiomyocytes. The results of the current study highlighted that GS-Rb1 could target miR-21 and its target gene, PDCD4, to protect OGD-injured cardiomyocytes. The results of the current study may provide a novel insight for the treatment of myocardial infarction with Traditional Chinese Medicines, involving miRs as targets.

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Impact of miR-208 and its Target Gene Nemo-Like Kinase on the Protective Effect of Ginsenoside Rb1 in Hypoxia/Ischemia Injuried Cardiomyocytes

Cited by 39 publications

References 35 publications

Circulating miR-181a as a Potential Novel Biomarker for Diagnosis of Acute Myocardial Infarction

Circulating miR-181a as a Potential Novel Biomarker for Diagnosis of Acute Myocardial Infarction

Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis Through miR-3546/SOX4/Survivin Axis in Rat Thy-1 Nephritis

Ginsenoside Rb1 protects cardiomyocytes from oxygen‑glucose deprivation injuries by targeting microRNA‑21

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