Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1157473 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcriptomic analysis of PPARalpha-dependent alterations during cardiac hypertrophy
| PRJNA113231 | ENA
Project description:Excess protein synthesis is the major pathological manifestation of cardiac hypertrophy; however, the underlying mechanism remains elusive. Here we found that a SAM transporter Slc25a26 translocated to mitochondria during cardiac hypertrophy. Silencing Slc25a26 aggravated phenylephrine-induced cardiomyocyte hypertrophy in neonatal rat ventricular myocytes. Transcriptome analysis revealed a specific regulation of ribosome genes by Slc25a26. Puromycin incorporation assay showed a negative regulation of protein synthesis rate by Slc25a26. The translational regulation was independent of ribosome assembly, but abolished by mTOR inhibitor rapamycin. Administration of SAM, or silencing Samtor, reversed the inhibitory impact of Slc25a26 on protein synthesis. AAV9-mediated Slc25a26 overexpression in mouse heart increased the SAM level in mitochondria, but reduced that in nucleus and cytoplasm. Transaortic-constriction-induced hypertrophic pathologies, including pathological gene induction, cardiomyocyte enlargement, myocardial remodeling and heart dysfunction were significantly alleviated by Slc25a26 overexpression. Our data demonstrate a crucial role of subcellular SAM homeostasis in translational control during cardiac hypertrophy.
2022-01-05 | GSE173737 | GEO
Project description:HOXA5 is important in overload-induced cardiac hypertrophy. We uesd RNA-Seq to detail global expression program alterations in adult mice cardiomyocytes transfected with Small interfering RNA (siN or siHoxa5 )and treated with phenylephrine(100μM) . Comparisons consisted of identifying Hoxa5-affected gene expression patterns.
2021-01-26 | GSE165497 | GEO
Project description:Zinc dyshomeostasis has been involved in the pathogenesis of cardiac hypertrophy; however, the dynamic regulation of intracellular zinc and its downstream signaling in cardiac hypertrophy remain largely unknown. Here we screened ZIP (SLC39) family members that were responsible for zinc uptake in a phenylephrine (PE)-induced cardiomyocyte hypertrophy model. We found that Slc39a2 was the only member that was altered at mRNA level by PE treatment in neonatal rat ventricular myocytes (NRVMs), but its protein level was not affected. Zincpyr1 staining showed a significant decrease in zinc uptake after PE treatment or after Slc39a2 knockdown in NRVMs, indicating an inhibition of its transport activity during hypertrophy. Slc39a2 deficiency caused spontaneous hypertrophy in NRVMs, and further exacerbated the hypertrophic responses after PE treatment. RNA sequencing analysis confirmed a largely aggravated pro-hypertrophic transcriptome reprogramming after Slc39a2 knockdown. Interestingly, the innate immune pathways, including NOD signaling, TOLL-like receptor, NFB, and IRFs, were substantially enriched after Slc39a2 knockdown. Whereas IRF7, the most sensitive among all IRFs, did not mediate the effect of Slc39a2 in hypertrophy, pro-hypertrophy phosphorylations of NFB and STAT3 were significantly enhanced after Slc39a2 knockdown, in parallel with degradation of IkBα protein. Our data demonstrate that SLC39A2-mediated zinc homeostasis contributes to the remodeling of innate immune signaling in cardiomyocyte hypertrophy, and provide novel insights into the pathogenesis of heart failure and its treatment.
2021-11-24 | GSE175884 | GEO
Project description:Pressure overload induces a transition from cardiac hypertrophy to heart failure, but its underlying mechanisms remain elusive. Here we reconstruct a trajectory of cardiomyocyte remodeling and clarify distinct cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure, by integrating single-cardiomyocyte transcriptome with cell morphology, epigenomic state and heart function. During early hypertrophy, cardiomyocytes activate mitochondrial translation/metabolism genes, whose expression is correlated with cell size and linked to ERK1/2 and NRF1/2 transcriptional networks. Persistent overload leads to a bifurcation into adaptive and failing cardiomyocytes, and p53 signaling is specifically activated in late hypertrophy. Cardiomyocyte-specific p53 deletion shows that cardiomyocyte remodeling is initiated by p53-independent mitochondrial activation and morphological hypertrophy, followed by p53-dependent mitochondrial inhibition, morphological elongation, and heart failure gene program activation. Human single-cardiomyocyte analysis validates the conservation of the pathogenic transcriptional signatures. Collectively, cardiomyocyte identity is encoded in transcriptional programs that orchestrate morphological and functional phenotypes.
2018-07-30 | GSE95142 | GEO
Project description:Slc39a2-mediated Zinc Homeostasis Modulates Innate Immune Signaling in Phenylephrine-induced Cardiomyocyte Hypertrophy
| PRJNA734256 | ENA
Project description:We compared the transcriptome modified by siRNA-mediated cardiac hypertrophy associated epigenentic regulator (Chaer) with negative control siRNA treated neonatal rat ventricular myocytes with or without phenylephrine treatment. The results suggest that Chaer knockdown broadly blocks the phenylephrine-induced hypertrophic programming of the transcriptome. Transcripts profiles from neonatal rat ventricular myocytes with or without phenylephrine and with or without Chaer-specific siRNA compared to negative control siRNA
2016-06-30 | E-GEOD-82339 | biostudies-arrayexpress
Project description:Pathological growth of cardiomyocytes during hypertrophy is characterized by excess protein synthesis; however, the regulatory mechanism remains largely unknown. Using a neonatal rat ventricular myocyte (NRVMs) model, here we find that the expression of nucleosome assembly protein 1 like 5 (Nap1l5) is upregulated in phenylephrine (PE)-induced hypertrophy. Knockdown of Nap1l5 expression by siRNA significantly blocks cell size enlargement and pathological gene induction after PE treatment. In contrast, Adenovirus-mediated Nap1l5 overexpression significantly aggravates the pro-hypertrophic effects of PE on NRVMs. RNA-seq analysis reveals that Nap1l5 knockdown reverses the pro-hypertrophic transcriptome reprogramming after PE treatment. Whereas immune response is dominantly enriched in the upregulated genes, oxidative phosphorylation, cardiac muscle contraction and ribosome related pathways are remarkably enriched in the down-regulated genes. Although PRC2 and PRC1 are involved in Nap1l5-mediated gene regulation, Nap1l5 does not directly alter the levels of global histone methylations. However, puromycin incorporation assay shows that Nap1l5 is both necessary and sufficient to drive the increased protein synthesis rate in cardiomyocyte hypertrophy. This is attributable to a direct regulation of ribosome assembly by Nap1l5. Our findings demonstrate a previously unrecognized role of Nap1l5 in translation control during cardiac hypertrophy.
2022-10-09 | GSE185699 | GEO
Project description:We compared the transcriptome modified by siRNA-mediated cardiac hypertrophy associated epigenentic regulator (Chaer) with negative control siRNA treated neonatal rat ventricular myocytes with or without phenylephrine treatment. The results suggest that Chaer knockdown broadly blocks the phenylephrine-induced hypertrophic programming of the transcriptome.
2016-06-30 | GSE82339 | GEO
Project description:Pressure overload induces a transition from cardiac hypertrophy to heart failure, but its underlying mechanisms remain elusive. Here we reconstruct a trajectory of cardiomyocyte remodeling and clarify distinct cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure, by integrating single-cardiomyocyte transcriptome with cell morphology, epigenomic state and heart function. During early hypertrophy, cardiomyocytes activate mitochondrial translation/metabolism genes, whose expression is correlated with cell size and linked to ERK1/2 and NRF1/2 transcriptional networks. Persistent overload leads to a bifurcation into adaptive and failing cardiomyocytes, and p53 signaling is specifically activated in late hypertrophy. Cardiomyocyte-specific p53 deletion shows that cardiomyocyte remodeling is initiated by p53-independent mitochondrial activation and morphological hypertrophy, followed by p53-dependent mitochondrial inhibition, morphological elongation, and heart failure gene program activation. Human single-cardiomyocyte analysis validates the conservation of the pathogenic transcriptional signatures. Collectively, cardiomyocyte identity is encoded in transcriptional programs that orchestrate morphological and functional phenotypes.
2018-07-30 | GSE95140 | GEO