Mus musculus
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ABSTRACT:
PROVIDER: PRJNA280998 | ENA |
REPOSITORIES: ENA
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Project description:miR-182 modulates myocardial hypertrophic response induced by angiogenesis in heart
| PRJNA280996 | ENA
Project description:miR-182 modulates myocardial hypertrophic response induced by angiogenesis in heart (MoGene)
| PRJNA280997 | ENA
Project description:Angiogenesis induced by placental growth factor (PlGF) in heart promotes myocardial hypertrophy through the paracrine action of endothelium-derived nitric oxide which triggers the degradation of RGS4 and subsequent the activation of Akt/mTORC1 pathway in cardiomyocytes. However, whether alterations in miRNAs contribute to the development of hypertrophy is largely undetermined. We found that miR-182 contributed to the hypertrophic response and activation of Akt/mTORC1 pathway by suppressing the expression of Bcat2, Pink1, Adcy6, Foxo3. miR-182 targeted genes were investigated in the mouse model of myocardial angiogenesis induced by conditional, cardiac specific expression of PlGF. We also induced angiogenesis, but blocked hypertrophy by concomitant expression of PlGF and RGS4 (PlGF/RGS4 mice). The mRNA expression profiling in PlGF and PlGF/RGS4 mice were assessed after 6 weeks of transgene expression, concurent with the development of myocardial hypertrophy.
2016-02-17 | E-GEOD-67815 | biostudies-arrayexpress
Project description:Angiogenesis induced by placental growth factor (PlGF) in heart promotes myocardial hypertrophy through the paracrine action of endothelium-derived nitric oxide which triggers the degradation of RGS4 and subsequent activation of the Akt/mTORC1 pathway in cardiomyocytes. However, whether alterations in miRNAs contribute to the development of hypertrophy is largely undetermined. We found that miR-182 contributed to the hypertrophic response and activation of the Akt/mTORC1 pathway by suppressing the expression of Bcat2, Pink1, Adcy6, Foxo3. The expression of miRNAs and the effects of anti-miRs were investigated in the mouse model of myocardial angiogenesis induced by conditional, cardiac specific expression of PlGF. We also induced angiogenesis, but blocked hypertrophy by concomitant expression of PlGF and RGS4 (PlGF/RGS4 mice). Microarray profiling of miRNAs in LV myocardium was determined after 3 and 6 weeks of transgene expression.
2016-02-17 | E-GEOD-67814 | biostudies-arrayexpress
Project description:Angiogenesis induced by placental growth factor (PlGF) in heart promotes myocardial hypertrophy through the paracrine action of endothelium-derived nitric oxide which triggers the degradation of RGS4 and subsequent activation of the Akt/mTORC1 pathway in cardiomyocytes. However, whether alterations in miRNAs contribute to the development of hypertrophy is largely undetermined. We found that miR-182 contributed to the hypertrophic response and activation of the Akt/mTORC1 pathway by suppressing the expression of Bcat2, Pink1, Adcy6, Foxo3.
2016-02-17 | GSE67814 | GEO
Project description:Angiogenesis induced by placental growth factor (PlGF) in heart promotes myocardial hypertrophy through the paracrine action of endothelium-derived nitric oxide which triggers the degradation of RGS4 and subsequent the activation of Akt/mTORC1 pathway in cardiomyocytes. However, whether alterations in miRNAs contribute to the development of hypertrophy is largely undetermined. We found that miR-182 contributed to the hypertrophic response and activation of Akt/mTORC1 pathway by suppressing the expression of Bcat2, Pink1, Adcy6, Foxo3.
2016-02-17 | GSE67815 | GEO
Project description:Background: Pathological upregulation of G protein-coupled receptor kinase 2 (GRK2) is a hallmark of heart failure and contributes to maladaptive signaling, hypertrophic remodeling, and cardiomyocyte death. MicroRNAs (miRNAs) are key post-transcriptional regulators of cardiac stress responses, however whether GRK2 is subject to miRNA targeting has not yet been fully established. Objective: We investigated potential miR-181a-mediated regulation of GRK2 in cardiomyocytes to better understand its effects on cardiac stress responses. Methods: miRNA microarray profiling was performed on mouse hearts two weeks after myocardial infarction. Bioinformatic target prediction analysis identified candidate miRNAs that are predicted to bind GRK2 in the 3’ untranslated region (UTR). Direct binding was assessed using luciferase reporter assays, and miR-181a was selected as the miRNA of interest to further pursue mechanistic and functional validation. miR-181a was overexpressed or inhibited in neonatal rat ventricular myocytes (NRVMs) and exposed to several modes of cellular stress to induce hypertrophy, hypoxia, and accumulation of reactive oxygen species. GRK2 expression, hypertrophic remodeling, oxidative stress, cell viability, and cyclic AMP (cAMP) signaling were assessed using quantitative PCR, immunoblotting, fluorescence imaging, and biochemical assays. Results: miR-181a directly targeted the GRK2 3′UTR and suppressed GRK2 expression at both mRNA and protein levels. miR-181a overexpression attenuated stress-induced hypertrophic gene expression, reduced cardiomyocyte cell size, decreased oxidative stress, improved survival under hypoxia, and enhanced cAMP production under β-AR stimulation. Conversely, inhibition of miR-181a resulted in sustained GRK2 expression, exacerbated hypertrophic signaling, and decreased cAMP production. Conclusion: These findings identify miR-181a as a functional post-transcriptional regulator of GRK2 that limits maladaptive signaling, hypertrophic remodeling, and cardiomyocyte injury. miR-181a-mediated GRK2 inhibition represents a potential therapeutic strategy for mitigating pathological signaling in heart failure.
2026-04-22 | GSE317550 | GEO
Project description:Aims: Mesenchymal stem cells (MSCs) gradually become attractive candidates for cardiac inflammation modulation, yet understanding of the mechanism remains elusive. Strikingly, recent studies indicated that exosomes secreted by MSCs might be a novel mechanism for the beneficial effect of MSCs transplantation after myocardial infarction. We therefore explored the role of MSC-derived exosomes (MSC-Exo) in the immunomodulation of macrophages after myocardial ischemia-reperfusion and its implications in cardiac injury repair. Methods and Results: Exosomes were isolated from the supernatant of MSCs using a gradient centrifugation method. Administration of MSC-Exo through intramyocardial injection after myocardial ischemia reperfusion reduced infarct size and alleviated inflammation level in heart and serum. Systemic depletion of macrophages with clodronate liposomes abolished the curative effects of MSC-Exo. MSC-Exo modified the polarization of M1 macrophages to M2 macrophages both in vivo and in vitro. miRNA-sequencing of MSC-Exo and bioinformatics analysis implicated miR-182 as a potent candidate mediator of macrophage polarization and TLR4 as a downstream target. Diminishing miR-182 in MSC-Exo partially attenuated its modulation of macrophage polarization. Likewise, knock down of TLR4 also conferred cardioprotective efficacy and reduced inflammation level in a mouse model of myocardial ischemia/reperfusion. Conclusion: Our data indicates that MSC-Exo attenuates myocardial ischemia/reperfusion injury via shuttling miR-182 that modifies the polarization state of macrophages. This study sheds new light on the application of MSC-Exo a potential therapeutic tool for myocardial ischemia/reperfusion injury.
2021-09-01 | GSE120149 | GEO
Project description:Evidence from epidemiological and mechanistic studies suggests that a variety of cardiovascular diseases are associated with tumour development. However, which cell types in the diseased heart are involved in the promotion of tumour progression remains poorly understood. In this study, the role of exosomes from hypertrophic cardiomyocytes in tumour progression was investigated. A model of cardiac hypertrophy was generated in mice using transverse aortic constriction (TAC). Breast cancer cells were then implanted in model animals. Exosomes derived from AC16 cardiomyocytes treated with Ang II to induce hypertrophic growth were subsequently injected into nude mice in which breast cancer cells had previously been implanted. The results showed that exosomes from hypertrophic cardiomyocytes promoted breast cancer progression. Furthermore, transcriptome sequencing and mass spectrometric analysis demonstrated that miR-362-5p, S100A7, and S100A8 were upregulated in exosomes derived from Ang II-treated AC16 cells, which promoted the proliferation, invasion, and migration of breast cancer cells. A retrospective clinical study showed that the expression of miR-362-5p, S100A7, and S100A8 was increased in plasma exosomes obtained from patients with cardiac hypertrophy. Notably, the levels of the three factors were observed to be associated with the extent of inflammation in patients with myocardial hypertrophy. Hypertrophic cardiomyocytes promote breast cancer progression through exosomes, and this effect is mediated by S100A7, S100A8, and miRNA-362-5p contained in the exosomes released from these cells.
2026-03-24 | PXD062164 | Pride
Project description:To identify genes differentially modulated by anti-miR-182 treatment in a liver melanoma metastasis mouse model. Targeting oncogenic microRNAs is emerging as a promising strategy for cancer therapy. Here we provide proof-of-principle for the safety and efficacy of miRNA targeting against metastatic tumors. We tested the effect of targeting miR-182, a pro-metastatic miRNA frequently overexpressed in melanoma, whose silencing represses invasion and induces apoptosis in vitro. In particular, we assessed the effect of anti-miR-182 oligonucleotides synthesized with 2’ sugar modifications and a phosphorothioate backbone in a mouse model of melanoma liver metastasis. Luciferase imaging showed that mice treated with anti-miR-182 had an appreciably lower burden of liver metastases compared to the control. We confirmed that miR-182 levels were effectively downregulated in the anti-miR treated tumors relative to the scrambled treated tumor both in the liver and in the spleen. This downregulation was accompanied by an upregulation of miR-182 direct targets. Transcriptome analysis of mouse tissues treated with anti-miR-182 or scramble oligonucleotides revealed an enrichment for genes controlling survival, adhesion and migration modulated in response to anti-miR-182 treatment. These data indicate that in vivo administration of anti-miRs allows for efficient miRNA targeting and concomitant upregulation of target levels. Our results suggest that the use of anti-miR-182 is a promising therapeutic strategy for metastatic melanoma and provide solid proof-of-principle for similar strategies against other metastatic tumors. Keywords: Differentially expressed genes (mRNAs) in response to miRNA inhibition
2010-10-21 | GSE24824 | GEO