Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA111285 | ENA |
REPOSITORIES: ENA
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Project description:Background: We have previously found that overexpression of CHF1/Hey2 in the myocardium prevents the development of phenylephrine-induced hypertrophy and promotes physiological hypertrophy in an aortic banding model. To identify transcriptional pathways regulated by CHF1/Hey2 in hypertrophy, we cultured primary neonatal mouse cardiac myocytes from wild type and transgenic mice overexpressing CHF1/Hey2 and treated them with serum, a potent hypertrophic stimulus. We determined transcriptional profiles by hybridization to Affymetrix GeneChip® Mouse Gene 1.0 ST Arrays. We identified important biological processes regulated by CHF1/Hey2 by Gene Set Analysis using Biological Process Gene Sets from the Gene Ontology Consortium. Results: We found that overexpression of CHF1/Hey2 suppresses gene sets involved in water transport, regulation of adenylate cyclase activity, embryonic eye morphogenesis, gut development and fluid transport after serum stimulation. Genes involved in protein dephosphorylation, in contrast, demonstrate increased expression in myocytes overexpressing CHF1/Hey2, and this increase is independent of serum treatment. Genes overexpressed prior to serum treatment are involved in regulation of transcription factor activity, protein export from the nucleus, and steroid hormone receptor signaling. Genes overexpressed after serum treatment are involved in autophagy, apoptosis and mitochondrial biogenesis. Conclusions: CHF1/Hey2 suppresses fluid transport, activation of adenylate cyclase activity, promotes phosphatase activity, autophagy and regulates other important biological processes likely relevant to hypertrophy. Transgenic Mice and Neonatal Mouse Myocyte Culture: WT no serum, 5; WT with serum, 7; TG no serum, 6; TG with serum, 7.
2010-04-08 | E-GEOD-14288 | biostudies-arrayexpress
Project description:Background: We have previously found that overexpression of CHF1/Hey2 in the myocardium prevents the development of phenylephrine-induced hypertrophy and promotes physiological hypertrophy in an aortic banding model. To identify transcriptional pathways regulated by CHF1/Hey2 in hypertrophy, we cultured primary neonatal mouse cardiac myocytes from wild type and transgenic mice overexpressing CHF1/Hey2 and treated them with serum, a potent hypertrophic stimulus. We determined transcriptional profiles by hybridization to Affymetrix GeneChip® Mouse Gene 1.0 ST Arrays. We identified important biological processes regulated by CHF1/Hey2 by Gene Set Analysis using Biological Process Gene Sets from the Gene Ontology Consortium. Results: We found that overexpression of CHF1/Hey2 suppresses gene sets involved in water transport, regulation of adenylate cyclase activity, embryonic eye morphogenesis, gut development and fluid transport after serum stimulation. Genes involved in protein dephosphorylation, in contrast, demonstrate increased expression in myocytes overexpressing CHF1/Hey2, and this increase is independent of serum treatment. Genes overexpressed prior to serum treatment are involved in regulation of transcription factor activity, protein export from the nucleus, and steroid hormone receptor signaling. Genes overexpressed after serum treatment are involved in autophagy, apoptosis and mitochondrial biogenesis. Conclusions: CHF1/Hey2 suppresses fluid transport, activation of adenylate cyclase activity, promotes phosphatase activity, autophagy and regulates other important biological processes likely relevant to hypertrophy.
2010-01-04 | GSE14288 | GEO
Project description:Transgenic mice with cardiac-restricted overexpression of connective tissue growth factor (CTGF) have substantially increased tolerance towards ischemia/reperfusion injury. In the transgenic mouse model, we found that CTGF induces expression of severeal genes putatively involved in cardioprotection. The purpose of this study was to determine gene expression in cardiac myocytes stimulated with purified, recombinant CTGF, comparing unstimulated and stimulated samples. The cytoprotective actions of CTGF was recflected in the transcriptome of CTGF-stimulated cardiac myocytes. Gene ontology analysis revealed that genes included under the terms anti-apoptosis, response to wounding, and response to stress were significantly overrepresented in cardiac myocytes exposed to CTGF. Serveral of the most higly up-regulated genes have previously been reported to exert cardioprotective actions and increase tolerance towards ischemia/reperfusion injury. Primary, adult cardiac myocytes were cultured in the absence (n=6) or presence (n=6) of 200 nmol/L recombinant CTGF for 48 hours.
2015-02-01 | E-GEOD-36073 | biostudies-arrayexpress
Project description:Transgenic mice with cardiac-restricted overexpression of connective tissue growth factor (CTGF) have substantially increased tolerance towards ischemia/reperfusion injury. In the transgenic mouse model, we found that CTGF induces expression of severeal genes putatively involved in cardioprotection. The purpose of this study was to determine gene expression in cardiac myocytes stimulated with purified, recombinant CTGF, comparing unstimulated and stimulated samples. The cytoprotective actions of CTGF was recflected in the transcriptome of CTGF-stimulated cardiac myocytes. Gene ontology analysis revealed that genes included under the terms anti-apoptosis, response to wounding, and response to stress were significantly overrepresented in cardiac myocytes exposed to CTGF. Serveral of the most higly up-regulated genes have previously been reported to exert cardioprotective actions and increase tolerance towards ischemia/reperfusion injury.
2015-02-01 | GSE36073 | GEO
Project description:The nuclear acetyltransferase p300 is a dose-dependent and limiting regulator of cardiac hypertrophy. p300 regulates hypertrophy by controlling the expression of specific microRNAs.The objective of this study was to dissect the role of miR-142 during p300 regulated hypertophic growth in vitro and in vivo and to verify its targets. MiR142 and a non target control were overexpressed using lentivirus in primary culture of neonatal cardiac myocytes. Overexpression was checked 48 hour post transfection. Samples include miR142 OE and non target from three different experiments.
2012-03-07 | E-GEOD-31121 | biostudies-arrayexpress
Project description:Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disorder, characterized by cardiomyocyte hypertrophy, cardiomyocyte disarray and fibrosis, which has a prevalence of ~1:200-500 and predisposes individuals to sudden death and heart failure. The mechanisms through which diverse HCM-causing mutations cause cardiac dysfunction remain mostly unknown and their identification may reveal new therapeutic avenues. MicroRNAs have emerged as critical regulators of gene expression and disease phenotype in various pathologies. We explored whether miRNAs could play a role in HCM pathogenesis and offer potential therapeutic targets. Methods and Results: Using high-throughput miRNA expression profiling and qPCR analysis in two distinct mouse models of HCM, we found that miR-199a-3p expression levels are upregulated in mutant mice compared to age- and treatment-matched wild-type mice. We also found that miR-199a-3p expression is enriched in cardiac non-myocytes compared to cardiomyocytes. When we expressed miR-199a-3p mimic in cultured primary cardiac non-myocytes and analyzed the conditioned media by proteomics, we found that several ECM proteins (e.g., TSP2, FBLN3, COL11A1, LYOX) were differentially expressed. We confirmed our proteomics findings by qPCR analysis of selected mRNAs and demonstrated that miR-199a-3p mimic expression in cardiac non-myocytes drives upregulation of ECM genes including Tsp2, Fbln3, Pcoc1, Col1a1 and Col3a1. To examine the role of miR-199a-3p in vivo, we inhibited its function using lock-nucleic acid (LNA)-based inhibitors (antimiR-199a-3p) in an HCM mouse model. Our results revealed that progression of cardiac fibrosis is attenuated when miR-199a-3p function is inhibited in mild-to-moderate HCM. Finally, guided by computational target prediction algorithms, we identified mRNAs Cd151 and Itga3 as direct targets of miR-199a-3p and have shown that miR-199a-3p mimic expression negatively regulates AKT activation in cardiac non-myocytes. Conclusions: Altogether, our results suggest that miR-199a-3p may contribute to cardiac fibrosis in HCM through its actions in cardiac non-myocytes. Thus, inhibition of miR-199a-3p in mild-to-moderate HCM may offer therapeutic benefit in combination with complementary approaches that target the primary defect in cardiac myocytes.
2024-01-26 | PXD042904 | Pride
Project description:We report gene expression changes after knockdown of transcription factors in human iPSC-derived cardiac myocytes. In prior experiments we showed that transcription factors known to be important for cardiac development were frequently up-regulated (i.e., "responsive") after small molecule perturbations of cultured iPSC-derived cardiac myocytes. We used RNA sequencing to test whether siRNA-mediated knockdown of transcription factors with different perturbation-responsiveness and tissue-specificity profiles would lead to inappropriate up-regulation of non-myocyte gene sets in cardiac myocytes.
2021-02-17 | GSE166823 | GEO
Project description:Growth differentiating factor (GDF)15 is a TGFβ superfamily cytokine and a reported biomarker of heart failure. Myocardial expression of GDF15 is increased in heart failure. Yet, the mechanisms that control synthesis and release of GDF15 as well as the autocrine/paracrine functions of GDF15 on fibroblast function is lacking. Thus, the aim of this study was to investigate signaling pathways and functions of GDF15 in cardiac fibroblasts. Cardiac fibroblasts and cardiac myocytes were isolated from adult C57/BL6 mice, maintained in primary culture and stimulated with recombinant (r)GDF15 or recombinant (r)CCN2. Short-term stimulation (30 minutes) of cardiac fibroblasts demonstrated a GDF15-induced activation of several intracellular signaling pathways including a concentration-dependent increase of phospho-Smad3(Ser423/425) (p<0.05, n=3), phospho-AKT(Ser473) (p<0.05, n=3) and phospho-IκBα(Ser32/36) (p<0.05, n=3) levels. However, rGDF15 did not phosphorylate Smad3(Ser423/425) or IκBα(Ser32/36) in cardiac myocyte. Cardiac fibroblasts exposed to rGDF15 for 48 hours displayed differentiation towards myofibroblasts reflected by increased levels of the differentiation marker α-smooth muscle actin (SMA) similar to cardiac fibroblasts stimulated with TGFβ. The effect of GDF15 on α-SMA was dose-dependent ranging from 500 nM - 20 nM rGDF15 (p<0.05, n=3). Differentiation towards a myofibroblast phenotype in the presence of GDF15 was also supported by higher matrix metalloproteinase (MMP) enzyme activity in the cell culture medium (6±1 fold increase, n=3, p<0.05) and increased expression and release of MMP-3, 9 and 13. Immunoreactive GDF15 was predominantly found in cardiac myocytes. Recombinant CCN2 substantially induced GDF15 expression in cardiac myocytes, but not in cardiac fibroblasts. In conclusion, our data demonstrate that GDF15 is a paracrine factor in myocardial tissue and specifically regulated by CCN2 in cardiac myocytes. GDF15 has similar effects as TGFβ on fibroblasts by activation of intracellular signaling pathways and differentiation to a myofibroblasts phenotype.
2017-02-19 | GSE55252 | GEO
Project description:Primary neonatal rat cardiac myocytes were isolated and subjected to siRNA mediated Yap knockdown
2019-07-04 | GSE121929 | GEO
Project description:Primary neonatal rat cardiac myocytes or fibroblasts were isolated and subjected to siRNA mediated Yap knockdown
2018-10-30 | GSE112464 | GEO