The role of cardiomyocyte Muscle Ring Finger-1 (MuRF1) in transcriptional responses to cyclic stretch (Wei HL1 str RNA seq oridata 71917)
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ABSTRACT:
PROVIDER: PRJNA484903 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7652880_1.fastq.gz | Fastqsanger.gz | |||
| SRR7652880_2.fastq.gz | Fastqsanger.gz | |||
| SRR7652890_1.fastq.gz | Fastqsanger.gz | |||
| SRR7652890_2.fastq.gz | Fastqsanger.gz | |||
| SRR7652900_1.fastq.gz | Fastqsanger.gz |
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Project description:We investigated the role of cardiomyocyte MuRF1 in the transcriptional responses to cyclic stretch (15% biaxial stretch at 1 Hz for 60 min) using the HL-1 cell line.
2021-08-10 | GSE118229 | GEO
Project description:We previously identified a role for the muscle-specific ubiquitin ligase MuRF1 (Muscle Ring Finger-1) in cardiac ischemia-reperfusion (I/R) injury. We found that cardiomyocyte-specific (alphaMHC-) MuRF1 transgenic mice (MuRF1 Tg+) mice were significantly protected from I/R injury. As we discovered MuRF1’s regulation of other transcriptions factors, we sought to identify other ways in which MuRF1 was cardioprotective in I/R injury. In the present study, we first identified the regulation of MuRF1 expression by qPCR in a porcine model of I/R injury. MuRF1 mRNA significantly increased within 90 minutes of I/R injury. We next assayed MuRF1 Tg+ ventricular tissue after I/R reperfusion injury by microarray (44K transcripts) to identify how MuRF1 regulates the transcriptome. We identified 71 significantly altered genes having a >1.5-fold (p<0.01) in MuRF1 Tg+ and wildtype hearts challenged with I/R injury (or sham operation). Functional annotation of the top upregulated genes found enrichment for myogenesis, cell adhesion, and nucleic acid metabolism. TRANSFAC analysis of MuRF1 Tg+ significant genes identified enrichment for genes (30-53%) with promoter regions recognized by the transcription factors MAZ, PIT1, VMW65, and BACH2. The transcription factor MAZ binds muscle creatine kinase (MCK) promoter in skeletal and cardiac myocytes, known most for its regulation of myogenin and MEF2C in cardiomyocytes. While the role of PIT1 and BACH2 in adult cardiomyocytes is not clear, VMW65 is a powerful transactivator with functions in chromatin remodeling. In neonatal cardiomycoyte I/R injury, VMW65 associates with HIF1alpha to upregulate cardioprotective VEGF, Glut-1, Glut-4, HSP70, and iNOS expression. These findings elucidate the MuRF1-specific regulation of genes in cardiac I/R injury that are associated with cardioprotection and may represent multiple additional direct or indirect mechanisms that MuRF1 regulates cardiomyocyte signaling.
2019-01-05 | GSE108940 | GEO
Project description:Muscle ring finger (MuRF) proteins have been implicated in the transmission of mechanical forces to nuclear cell signaling pathways through their association with the sarcomere. We recently reported that MuRF1, but not MuRF2, regulated pathologic cardiac hypertrophy in vivo. This was surprising since MuRF1 and MuRF2 interact redundantly with sarcomeric proteins in yeast two hybrid studies, and form both homo- and hetero-dimers with each other. To determine if MuRF1 and MuRF2 were functionally redundant during development, we created mice lacking either 3 or 4 of the MuRF1 and MuRF2 alleles and compared them functionally. Surprisingly, only mice missing all four MuRF1 and MuRF2 alleles (MuRF1-/-//MuRF2-/-) developed a spontaneous hypertrophic cardiomyopathy - mice that were null for one of the genes, but heterozygous for the other (i.e. MuRF1-/-//MuRF2+/- or MuRF1+/-//MuRF2-/-) were phenotypically identical to wild type mice. Electron microscopy of the hearts of MuRF1-/-//MuRF2-/-(MuRF1/MuRF2 DN) mice identified altered Z disc and M line architecture, and a distinct swelling of mitochondria. MuRF1-/-//MuRF2-/- mouse hearts displayed increased expression of genes associated with fetal cardiac metabolism, including smooth muscle actin and b myosin heavy chain, suggesting that the cardiac hypertrophy seen in these mice was associated with a reversion to a fetal gene program. Despite our prediction that we would also see an increase in glucose compared to fatty acid oxidation (another trait of fetal cardiac metabolism) we saw that MuRF1-/-//MuRF2-/- heart homogenates oxidized significantly less glucose compared to controls, suggesting an important role for MuRF1 and MuRF2 in the regulation of glucose metabolism in vivo. This study identifies a previously unreported redundancy in the function of MuRF proteins in normal cardiac development. Keywords: Genetic modification.
2013-04-01 | GSE14512 | GEO
Project description:Muscle ring finger (MuRF) proteins have been implicated in the transmission of mechanical forces to nuclear cell signaling pathways through their association with the sarcomere. We recently reported that MuRF1, but not MuRF2, regulated pathologic cardiac hypertrophy in vivo. This was surprising since MuRF1 and MuRF2 interact redundantly with sarcomeric proteins in yeast two hybrid studies, and form both homo- and hetero-dimers with each other. To determine if MuRF1 and MuRF2 were functionally redundant during development, we created mice lacking either 3 or 4 of the MuRF1 and MuRF2 alleles and compared them functionally. Surprisingly, only mice missing all four MuRF1 and MuRF2 alleles (MuRF1-/-//MuRF2-/-) developed a spontaneous hypertrophic cardiomyopathy - mice that were null for one of the genes, but heterozygous for the other (i.e. MuRF1-/-//MuRF2+/- or MuRF1+/-//MuRF2-/-) were phenotypically identical to wild type mice. Electron microscopy of the hearts of MuRF1-/-//MuRF2-/-(MuRF1/MuRF2 DN) mice identified altered Z disc and M line architecture, and a distinct swelling of mitochondria. MuRF1-/-//MuRF2-/- mouse hearts displayed increased expression of genes associated with fetal cardiac metabolism, including smooth muscle actin and b myosin heavy chain, suggesting that the cardiac hypertrophy seen in these mice was associated with a reversion to a fetal gene program. Despite our prediction that we would also see an increase in glucose compared to fatty acid oxidation (another trait of fetal cardiac metabolism) we saw that MuRF1-/-//MuRF2-/- heart homogenates oxidized significantly less glucose compared to controls, suggesting an important role for MuRF1 and MuRF2 in the regulation of glucose metabolism in vivo. This study identifies a previously unreported redundancy in the function of MuRF proteins in normal cardiac development. Keywords: Genetic modification. Four strain-matched groups of 12 week old mice were investigated: 1) MuRF1 -/- MuRF2 -/-; 2) MuRF1 +/+ MuRF2 +/+; 3) MuRF1 -/- MuRF2 +/-; 4) MuRF1 +/- MuRF2 -/-. Biological replicates: 4 WT, 4 MuRF1 -/- // MuRF2 -/-, 4 MuRF1 +/- //MuRF2 -/-, 4 MuRF1 -/- // MuRF2 +/-. Hearts harvested. One replicate per array.
2013-04-01 | E-GEOD-14512 | biostudies-arrayexpress
Project description:Under various pathophysiological muscle-wasting conditions like diabetes and starvation, a family of ubiquitin ligases, including MuRF1 (Muscle specific RING-Finger protein 1), are induced to target muscle proteins for degradation via ubiquitination. In an attempt to identify the in vivo targets of MuRF1 we have generated transgenic mouse lines overexpressing MuRF1 in a skeletal muscle specific fashion. MuRF1-TG lines were viable and had normal fertility. Characterization of their skeletal muscles did not reveal evidence for muscle wasting at 10 weeks of age. In this experiment we compared the skeletal muscle transcriptome of transgenic mice with wildtypes. Keywords: MuRF1 transgene overexpression
2008-05-15 | GSE10626 | GEO
Project description:Chromobacterium sp. HL1 isolate:HL1 Genome sequencing
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Project description:MuRF1 mediated ubiquitination of titin promotes autophagy machinery recruitment onto titin. Titin ubiquitination appears dynamically regulated by myofibrillar stretch via the unfolding of an NL linker sequence, leading to different ubiquitination patterns of the chain. This mechanism might be compromised in the titin SNP rs 200675195, a possible factor in cardiomyopathy.
2021-06-23 | PXD015340 | Pride
Project description:MuRF1 mediated ubiquitination of titin promotes autophagy machinery recruitment onto titin. Titin ubiquitination appears dynamically regulated by myofibrillar stretch via the unfolding of an NL linker sequence, leading to different ubiquitination patterns of the chain. This mechanism might be compromised in the titin SNP rs 200675195, a possible factor in cardiomyopathy.
2021-06-23 | PXD015339 | Pride
Project description:Lung cancer is one of the leading causes of death. However, most of the researches were based on the traditional cell-culturing method. Whereas cells of lung are subjected to the mechanical forces periodically while breathing. In the present study, we applied cyclic stretch to stimulate the continuously contracting physical condition. We uncovered the stretching force-induced phosphoproteome in lung cancer cell A549 and fibroblast IMR-90. 2048 and 2604 phosphosites corresponding to 837 and 1008 phosphoproteins were identified in A549 and IMR-90, respectively. Interestingly, cytoskeleton reorganization and mitochondrial localization were enriched in the significantly expressed phosphoproteins in response to cyclic stretch. Indeed, we found this physical stress changed cell alignment thus disrupted mitochondrial dynamics. We proved that mitochondrial fusion is induced by uniaxial stretch in 2 cell lines. This study reveals the molecular mechanism of cyclic stretch and supports that stretching force enhanced cellular rearrangement and mitochondrial fusion in lung cells.
2021-09-08 | PXD012010 | Pride
Project description:With gene expression profiling it was aimed to identify the differentially expressed genes associated with the regulation of the cytoskeleton to investigate the stretch-induced cell alignment mechanism. A whole genome microarray based analysis of the stretch-induced gene expression changes was done. Gene expression was measured at the beginning of the alignment process showing first reoriented cells after 5 h stretching and at the end after 24 h, where nearly all cells are aligned. Cyclic mechanical stretching of cells results in cellular alignment perpendicular to the stretch direction regulating cellular response. This stress response is assumed to be an adaptation mechanism to reduce extensive stretching but also acts as architectural restructuring changing performance and biomechanics of the tissue. Gene expression profiling of control vs. stretched primary human dermal fibroblasts after 5 h and 24 h demonstrated the regulation of differentially expressed genes associated with metabolism, differentiation and morphology.
2014-06-11 | GSE58389 | GEO