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MicroRNA-210 suppresses glucocorticoid receptor expression in response to hypoxia in fetal rat cardiomyocytes.

ABSTRACT: Hypoxia is a common intrauterine stressor, often resulting in intrauterine growth restriction and increased risk for cardiovascular disease later in life. The aim of this work was to test the hypothesis that microRNA-210 (miR-210) mediates the detrimental suppression of glucocorticoid receptor (GR) in response to hypoxia in fetal rat cardiomyocytes. Cardiomyocytes isolated from gestational day 21 Sprague Dawley fetal rats showed increased miR-210 levels and reduced GR abundance after exposure to ex vivo hypoxia (1% O2). In regard to mechanisms, the different contributions of hypoxia response elements (HREs) motifs in the regulation of miR-210 promoter activity and the miR-210-mediated repression of GR expression were determined in rat embryonic heart-derived myogenic cell line H9c2. Moreover, using a cell culture-based model of hypoxia-reoxygenation injury, we assessed the cytotoxic effects of GR suppression under hypoxic conditions. The results showed that hypoxia induced HIF-1?-dependent miR-210 production, as well as miR-210-mediated GR suppression, in cardiomyocytes. Furthermore, inhibition or knockdown of GR exacerbated cell death in response to hypoxia-reoxygenation injury. Altogether, the present study demonstrates that the HIF-1?-dependent miR-210-mediated suppression of GR in fetal rat cardiomyocytes increases cell death in response to hypoxia, providing novel evidence for a possible mechanistic link between fetal hypoxia and programming of ischemic-sensitive phenotype in the developing heart.

SUBMITTER: Martinez SR

PROVIDER: S-EPMC5655194 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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MicroRNA-210 suppresses glucocorticoid receptor expression in response to hypoxia in fetal rat cardiomyocytes.

Martinez Shannalee R SR Ma Qingyi Q Dasgupta Chiranjib C Meng Xianmei X Zhang Lubo L

Oncotarget 20170511 46

Hypoxia is a common intrauterine stressor, often resulting in intrauterine growth restriction and increased risk for cardiovascular disease later in life. The aim of this work was to test the hypothesis that microRNA-210 (miR-210) mediates the detrimental suppression of glucocorticoid receptor (GR) in response to hypoxia in fetal rat cardiomyocytes. Cardiomyocytes isolated from gestational day 21 Sprague Dawley fetal rats showed increased miR-210 levels and reduced GR abundance after exposure to ...[more]

PMID: 29113299

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Project description:Cardiac shock wave therapy (SWT) has been described as a novel therapeutic strategy that is able to alleviate myocardial ischemic injury. microRNA (miRNA/miR)?210 plays a cytoprotective role in cardiomyocytes in response to hypoxia by regulating cell apoptosis. The aim of the present study was to investigate whether cardiac SWT could protect cardiomyocytes from hypoxia?induced injury by regulating miR?210 expression. The murine adult cardiomyocyte cell line HL?1 was incubated for 5 h in hypoxic conditions, followed by reoxygenation for 12 h and treatment with SWT immediately following hypoxia in the present study. The cell viability was determined using an MTS assay. Western blot analyses were performed in order to detect cell signaling changes. Reactive oxygen species production was detected using dihydroethidium staining, and malondialdehyde levels were measured using the thiobarbituric acid method. miRNA and mRNA expression levels were confirmed via reverse transcription?quantitative PCR. Apoptosis was evaluated by means of flow cytometry. HL?1 cells were then transfected with miR?210 mimics or inhibitors in order to alter miR?210 expression levels, and the effects on HL?1 cells were determined. Hypoxia led to elevated oxidative stress, enhanced cell apoptosis and upregulated miR?210 expression levels in HL?1 cells, while SWT could alleviate hypoxia?induced cell injury and further promote miR?210 expression. miR?210 overexpression decreased apoptosis and oxidative stress during hypoxic stress in HL?1 cells, whereas inhibition of miR?210 increased cell apoptosis and promoted oxidative stress. Furthermore, miR?210 inhibition could reverse the effects of SWT on HL?1 cells. Finally, the mRNA analysis revealed that SWT significantly attenuated apoptosis?inducing factor mitochondrion?associated 3 and caspase 8 associated protein 2 mRNA expression levels in cardiomyocytes exposed to hypoxia, which were two targets of miR?210. SWT could exert cardioprotective effects against hypoxia?induced cardiac injury by modulating miR?210.

Dataset Information

MicroRNA-210 suppresses glucocorticoid receptor expression in response to hypoxia in fetal rat cardiomyocytes.

Publications

MicroRNA-210 suppresses glucocorticoid receptor expression in response to hypoxia in fetal rat cardiomyocytes.

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