MiR-182 modulates myocardial hypertrophic response induced by angiogenesis in heart
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus synthetic construct
PROVIDER: GSE67824 | GEO | 2016/02/17
SECONDARY ACCESSION(S): PRJNA280996
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-02-17 | E-GEOD-67824 | biostudies-arrayexpress
Project description:Myocardial hypertrophy is an adaptive response to hemodynamic demands. Although angiogenesis is critical to support the increase in heart mass with matching blood supply, it may also promote a hypertrophic response. Previously, we showed that cardiac angiogenesis induced by placental growth factor (PlGF), promotes myocardial hypertrophy through the paracrine action of endothelium-derived NO, which triggers the degradation of regulator of G protein signaling 4 (RGS4) to activate the Akt/mTORC1 pathways in cardiomyocytes. Here, we investigated whether miRNAs contribute to the development of hypertrophic response associated with myocardial angiogenesis. We show that miR-182 is upregulated concurrently with the development of hypertrophy in PlGF mice, but not when hypertrophy was blocked by concomitant expression of PlGF and RGS4, or by PlGF expression in eNOS(-/-) mice. Anti-miR-182 treatment inhibits the hypertrophic response and prevents the Akt/mTORC1 activation in PlGF mice and NO-treated cardiomyocytes. miR-182 reduces the expression of Bcat2, Foxo3 and Adcy6 to regulate the hypertrophic response in PlGF mice. Particularly, depletion of Bcat2, identified as a new miR-182 target, promotes Akt(Ser473)/p70-S6K(Thr389) phosphorylation and cardiomyocyte hypertrophy. LV pressure overload did not upregulate miR-182. Thus, miR-182 is a novel target of endothelial-cardiomyocyte crosstalk and plays an important role in the angiogenesis induced-hypertrophic response.
| S-EPMC4758045 | biostudies-literature
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 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 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: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:miR-182 modulates myocardial hypertrophic response induced by angiogenesis in heart
| PRJNA280996 | ENA
Project description:BackgroundHypoxia is a common feature of solid tumors, including HCC. And hypoxia has been reported to play an important role in HCC progression. However, the potential mechanism of miRNAs in hypoxia mediating HCC progression still remains unclear.MethodsThe HCC cells were cultured in the atmosphere of 1 % oxygen to induce hypoxia. The microRNA microarray was employed to search for the hypoxia-inducible miRNAs. RT-PCR, western blot and immunohistochemistry were used to detect the RNA and protein levels. HUVEC were applied to explore the angiogenesis level.ResultsWe found that miR-182 was upregulated in the hypoxia-based microarray. We then revealed that miR-182 was also significantly increased in the HCC tissues compared to the corresponding normal tissues. In vitro capilliary tube formation assays showed that the miR-182 promoted angiogenesis. RASA1 was demonstrated as the direct target of miR-182. In addition, the suppression of RASA1 phenocopied the pro-angiogenesis effects of miR-182. Besides, RASA1 was also decreased in the hypoxia HCC cells while the inhibition of miR-182 partially restored the level of RASA1.ConclusionsOur data showed that hypoxia regulated the expression of miR-182 and RASA1 to promote HCC angiogenesis.
| S-EPMC4493986 | biostudies-literature
Project description:Intermittent hypoxia (IH) is a feature of obstructive sleep apnea (OSA), a condition highly associated with hypertension-related cardiovascular diseases. Repeated episodes of IH contribute to imbalance of angiogenic growth factors in the hypertrophic heart, which is key in the progression of cardiovascular complications. In particular, the interaction between vascular endothelial growth factor (VEGF) and the kallikrein-kinin system (KKS) is essential for promoting angiogenesis. However, researchers have yet to investigate experimental models of IH that reproduce OSA, myocardial angiogenesis, and expression of KKS components. We examined temporal changes in cardiac angiogenesis in a mouse IH model. Adult male C57BI/6 J mice were implanted with Matrigel plugs and subjected to IH for 1-5 weeks with subsequent weekly histological evaluation of vascularization. Expression of VEGF and KKS components was also evaluated. After 3 weeks, in vivo myocardial angiogenesis and capillary density were decreased, accompanied by a late increase of VEGF and its type 2 receptor. Furthermore, IH increased left ventricular myocardium expression of the B2 bradykinin receptor, while reducing mRNA levels of B1 receptor. These results suggest that in IH, an unexpected response of the VEGF and KKS systems could explain the reduced capillary density and impaired angiogenesis in the hypoxic heart, with potential implications in hypertrophic heart malfunction.
| S-EPMC8123545 | biostudies-literature
Project description:Prostate cancer (PCa) is a clinically heterogeneous disease, where deregulation of epigenetic events, such as miRNA expression alterations, are determinants for its development and progression. MiR-182-5p, a member of the miR-183 family, when overexpressed has been associated with PCa tumor progression and decreased patients' survival rates. In this study, we determined the regulatory role of miR-182-5p in modulating aggressive tumor phenotypes in androgen-refractory PCa cell lines (PC3 and DU-145). The transient transfection of the cell lines with miR-182-5p inhibitor and mimic systems, significantly affected cell proliferation, adhesion, migration, and the viability of the cells to the chemotherapeutic agents, docetaxel, and abiraterone. It also affected the protein expression levels of the tumor progression marker pAKT. These changes, however, were differentially observed in the cell lines studied. A comprehensive biological and functional enrichment analysis and miRNA/mRNA interaction revealed its strong involvement in the epithelial-mesenchymal transition (EMT) process; expression analysis of EMT markers in the PCa transfected cells directly or indirectly modulated the analyzed tumor phenotypes. In conclusion, miR-182-5p differentially impacts tumorigenesis in androgen-refractory PCa cells, in a compatible oncomiR mode of action by targeting EMT-associated pathways.
| S-EPMC8961520 | biostudies-literature