MicroRNA-15b enhances hypoxia/reoxygenation-induced apoptosis of cardiomyocytes via a mitochondrial apoptotic pathway

Liu, Lifeng; Zhang, Guoming; Liang, Zhuo; Li, Xiuhua; Li, Tian-de; Fan, Junfen; Bai, Jing; Wang, Yu

doi:10.1007/s10495-013-0899-2

Cited by 63 publications

(48 citation statements)

References 34 publications

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“…Liu et al 17 primarily found that miRNA-15a/b was upregulated in response to cardiac I/R injury and correlated to myocardial apoptosis. The same authors further found that miRNA-15b deteriorated cardiomyocyte apoptosis by increasing the release of mitochondrial cytochrome c to the cytosol, resulting activation of caspase-3 and caspase-9, without affecting Bcl-2 mRNA 18. These studies suggested that miRNA-15b closely related to cardiomyocyte apoptosis after I/R.…”

Section: Introductionmentioning

confidence: 82%

MicroRNA-15b Deteriorates Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis by Downregulating Bcl-2 and MAPK3

Liu

Yang

Yin

et al. 2018

Journal of Investigative Medicine

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To investigate the role of miRNA-15b in cardiomyocyte apoptosis after ischemia reperfusion injury in acute myocardial infarction (AMI), we conducted the AMI rat model by using left anterior descending ligation and performed hypoxia/reoxygenation experiments in H9c2 cells. MiRNA-15b was measured by quantitative reverse transcription PCR (qRT-PCR). Cardiomyocyte apoptosis was determined by terminal deoxynucleotide transferase dUTP nick end labeling staining. Synthesized miRNA-15b mimic and inhibitor were transfected into H9c2 cells by Lipofectamine regent. RNA expression of B cell lymphoma/leukemia-2 (Bcl-2) and mitogen-activated protein kinase 3 (MAPK3) was examined by qRT-PCR and their protein expression was determined by western blot. Ischemia reperfusion increased miRNA-15b expression in the ischemic rat heart and resulted more severe cardiomyocytes apoptosis. In H9c2 cells, hypoxia/reoxygenation induced increased miRNA-15b expression and augmented cardiomyocyte apoptosis observed at 24 hours after 24-hour hypoxia. Compared with the vehicle group, miRNA-15b mimic further raised miRNA-15b level and increased cardiomyocyte apoptosis, whereas miRNA-15b inhibitor suppressed miRNA-15b expression and protected cardiomyocytes from apoptosis. Although the mRNA expression of the target genes Bcl-2 and MAPK3 was not changed significantly, the protein expression of these two genes were markedly reduced after miRNA-15b mimic treatment and significantly increased after transfected with miRNA-15b inhibitors. In conclusion, miRNA-15b deteriorates cardiomyocyte apoptosis by post-transcriptionally downregulating the expression of Bcl-2 and MAPK3.

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Section: Introductionmentioning

confidence: 82%

MicroRNA-15b Deteriorates Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis by Downregulating Bcl-2 and MAPK3

Liu

Yang

Yin

et al. 2018

Journal of Investigative Medicine

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“…A number of miRNAs, including miR-1 [15], miR-15b [16], miR-21 [17] and miR-145 [18], have been implicated in myocardial I/R injury due to their effects on key genes associated with apoptosis. MiR-92a has been implicated in myocardial I/R injury in variety of experimental models.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-92a Inhibition Attenuates Hypoxia/Reoxygenation-Induced Myocardiocyte Apoptosis by Targeting Smad7

Zhang

Zhou

et al. 2014

PLoS ONE

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BackgroundMicroRNAs (miRNAs) regulate a lot of physiological and pathological processes, including myocardial ischemia/reperfusion. Recent studies reported that knockdown of miR-92a could attenuate ischemia/reperfusion-induced myocardial injury. In the present study, we examined the potential anti-apoptotic effects of miR-92a in a rat myocardiocyte cell line, and the possible role of Smad7 in such actions.Methodology and ResultsIn a preliminary bioinformatic analysis, we identified SMAD family member 7 (Smad7) as a potential target for miR-92a. A luciferase reporter assay indeed demonstrated that miR-92a could inhibit Smad7 expression. Myocardial ischemia/reperfusion was simulated in rat H9c2 cells with 24-h hypoxia followed by 12-h reoxygenation. Prior to hypoxia/reoxygenation, cells were transfected by miR-92a inhibitor. In some experiments, cells were co-transfected with siRNA-Smad7. The miR-92a inhibitor dramatically reduced the release of lactate dehydrogenase and malonaldehyde, and attenuated cardiomyocyte apoptosis. The miR-92a inhibitor increased SMAD7 protein level and decreased nuclear NF-κB p65 protein. Effects of the miR-92a inhibitor were attenuated by co-transfection with siRNA-Smad7.ConclusionInhibiting miR-92a can attenuate myocardiocyte apoptosis induced by hypoxia/reoxygenation by targeting Smad7.

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“…Recombinant adenovirus was constructed as previously described (16). Briefly, the full length of CCN3 cDNA was amplified and subcloned into pAdTrack-CMV, an adenoviral shuttle plasmid.…”

Section: Construction Of Ccn3 Adenoviral Vectorsmentioning

confidence: 99%

Effects of CCN3 on fibroblast proliferation, apoptosis and extracellular matrix production

Ren

Hou

et al. 2014

International Journal of Molecular Medicine

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Abstract. CCN2 and CCN3 belong to the CCN family of proteins, which show a high level of structural similarity. Previous studies have shown that CCN2 mediates the ability of transforming growth factor (TGF)-β to stimulate collagen synthesis, leading to keloid formation. CCN2 and CCN3 are opposing factors in regulating the promoter activity and secretion of this extracellular matrix (ECM) protein. Thus, we hypothesize that CCN3 possesses an anti-scarring effect. However, the exact mechanism of CCN3 in this anti-scarring effect remains unclear. The aim of this study was to investigate the mechanism of CCN3 in reducing scar formation. Palatal fibroblasts were obtained from the explants of the oral palatal mucosa of 8-week-old male Sprague-Dawley rats. CCN3 overexpression vector was constructed and then transfected into cells. The inhibitory effects of CCN3 on cell growth were detected via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was measured using an Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) apoptosis detection kit and flow cytometry. The expression levels of collagen I, collagen III and α-smooth muscle actin (α-SMA) were determined by western blot analysis and RT-PCR. Following treatment with TGF-β1, we detected the expression of CCN3 and Smad1 in the fibroblasts. CCN3 significantly inhibited the growth and induction of apoptosis of fibroblasts. The expression of collagen I, collagen III and α-SMA was lower in the CCN3-transfected group as compared to the control and vector groups. TGF-β1 stimulation efficiently suppressed the expression of CCN3 at the mRNA and protein levels, and CCN3 was required for TGF-β1-induced Smad1 phosphorylation. Results of this study demonstrated that CCN3 is involved in the proliferation and apoptosis of fibroblasts and the synthesis of ECM proteins. Therefore, CCN3 may play an important role in the development of scar tissue, and may represent a novel therapeutic target for reducing scar formation.

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MicroRNA-15b enhances hypoxia/reoxygenation-induced apoptosis of cardiomyocytes via a mitochondrial apoptotic pathway

Cited by 63 publications

References 34 publications

MicroRNA-15b Deteriorates Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis by Downregulating Bcl-2 and MAPK3

MicroRNA-15b Deteriorates Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis by Downregulating Bcl-2 and MAPK3

MicroRNA-92a Inhibition Attenuates Hypoxia/Reoxygenation-Induced Myocardiocyte Apoptosis by Targeting Smad7

Effects of CCN3 on fibroblast proliferation, apoptosis and extracellular matrix production

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