Angiogenic potential of skeletal muscle derived extracellular vesicles differs between oxidative and glycolytic muscle
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA892113 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21973558.fastq.gz | Fastqsanger.gz | |||
| SRR21973559.fastq.gz | Fastqsanger.gz | |||
| SRR21973560.fastq.gz | Fastqsanger.gz | |||
| SRR21973561.fastq.gz | Fastqsanger.gz | |||
| SRR21973562.fastq.gz | Fastqsanger.gz |
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Project description:Skeletal muscle fibers regulate surrounding endothelial cells (EC) via secretion of numerous angiogenic factors, including extracellular vesicles (SkM-EV). Muscle fibers are broadly classified as oxidative (OXI) or glycolytic (GLY) depending on their metabolic characteristics. OXI fibers secrete more pro-angiogenic factors and have greater capillary densities than GLY fibers. OXI muscle secretes more EV than GLY, however it is unknown whether muscle metabolic characteristics regulate EV contents and signaling potential. Extracellular vesicles were isolated from primarily oxidative or glycolytic muscle tissue in mice. MicroRNA (miR) sequencing was done to determine SkM-EV miR contents and cultured endothelial cells were treated with OXI- and GLY-EV to investigate angiogenic signaling potential. There were considerable differences in miR contents between OXI- and GLY-EV and pathway analysis identified that OXI-EV miR were predicted to positively regulate multiple endothelial-specific pathways including nitric oxide (NO) and vascular endothelial growth factor (VEGF) pathways, compared to GLY-EV miRs. OXI-EV improved EC migration (+19%) and tube formation (length: +20%; # of tubes +35%) compared to GLY-EV. These benefits may have been NO pathway mediated, as OXI-EV increased phosphorylation of endothelial nitric oxide synthase (eNOS) and treatment of ECs with the NOS inhibitor L-NAME abolished differences in migration and tube formation between OXI- and GLY-EV. This is the first report to show widespread differences in miR contents between SkM-EV isolated from metabolically different muscle tissue and the first to demonstrate that oxidative muscle tissue secretes EV with greater angiogenic signaling potential than glycolytic muscle tissue.
2022-10-26 | GSE216121 | GEO
Project description:Skeletal muscle fibers regulate surrounding endothelial cells (EC) via secretion of numerous angiogenic factors, including extracellular vesicles (SkM-EV). Muscle fibers are broadly classified as oxidative (OXI) or glycolytic (GLY) depending on their metabolic characteristics. OXI fibers secrete more pro-angiogenic factors and have greater capillary densities than GLY fibers. OXI muscle secretes more EV than GLY, however it is unknown whether muscle metabolic characteristics regulate EV contents and signaling potential. EVs were isolated from primarily oxidative or glycolytic muscle tissue from mice. MicroRNA (miR) contents were determined and endothelial cells were treated with OXI- and GLY-EV to investigate angiogenic signaling potential. There were considerable differences in miR contents between OXI- and GLY-EV and pathway analysis identified that OXI-EV miR were predicted to positively regulate multiple endothelial-specific pathways, compared to GLY-EV. OXI-EV improved in vitro angiogenesis, which may have been mediated through nitric oxide synthase (NOS) related pathways, as treatment of endothelial cells with a non-selective NOS inhibitor abolished the angiogenic benefits of OXI-EV. This is the first report to show widespread differences in miR contents between SkM-EV isolated from metabolically different muscle tissue and the first to demonstrate that oxidative muscle tissue secretes EV with greater angiogenic signaling potential than glycolytic muscle tissue.
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Project description:FHL3 promotes the formation of fast glycolytic muscle fibers by interacting with YY1 and muscle glycolytic metabolism
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Project description:Composition of distinct muscle fiber types plays an important role in the regulation of skeletal muscle metabolism, as well as animal meat production.Four and a half LIM domain protein 3 (FHL3) is highly expressed in fast glycolytic muscle fibers and differentially regulates the expression of MyHC isoforms at cellular levels.Here we knocked out FHL3 in C2C12 cells by CRISPR/Cas9 technology.RNA sequencing analyses revealed that the expression of MYH7 in KO cells was significantly increased, while the expression of MYH1,MYH2 and MYH4 was significantly decreased.Further comfirm FHL3 regulates the transformation of muscle fiber types.
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Project description:The biochemical and functional differences between oxidative and glycolytic muscles affect human muscle health and animal meat quality, but the epigenetic regulation with respect to lncRNAs and circRNAs remains largely unknown. Here, we employed porcine oxidative and glycolytic skeletal muscles, at growth curve inflection point, to survey variant global lncRNAs and circRNAs expression using RNA-seq. In total, we obtained 540 million raw reads approximately 81.02 Gb of high quality data. After a strict filtering process, 4,046 lncRNAs were identified, including 911 differentially expressed lncRNAs (p < 0.05). The cis-regulatory analysis identified target genes that were enriched for specific GO terms and pathways (p < 0.05), including oxidation-reduction process, glycolytic process, fatty acid metabolic, PPAR signaling pathway, which are closely related to the different phenotypes between oxidative and glycolytic muscles. Additional, we also identified 810 circRNAs, 137 of them were differentially expressed (p < 0.05). The host genes of circRNAs were related to motor activity, transition between fast and slow fiber and ATP metabolic process by function enrichment analysis. Interestingly, we found circRNA290-miR27b-Foxj3 and circRNA9210-miR-23a-MEF2C taken as two competing endogenous network, which was closely linked to muscle fiber-type switching. circRNA41-miR-217-SIRT1 network was connected with mitochondria biogenesis in muscle. Furthermore, we found 44.69%, 39.19% and 54.01% of differentially expressed mRNAs, lncRNAs and circRNAs were siginificantly enriched pig QTL regions (traits of meat quality and growing development), respectively. Togeter, this study reveals a mass of candidate lncRNAs and circRNAs involved in muscle physiological function, which improve understanding of muscle metabolism and development from epigenetic perspectives.
2018-08-30 | GSE119137 | GEO
Project description:The physiological, biochemical and functional difference of oxidative and glycolytic muscles play important roles in human metabolic health as well as in meat quality of animal. To explore this aspect, we firstly provided a genome-wide landscape of DNA methylomes and their relationship with mRNA and miRNA transcriptome for PMM (psoas major muscle; oxidative) and LDM (longissimus dorsi muscle; glycotic) in this study. We observed hypomethylation of subtelomeric regions and high mitochondria content contributed to fast replicative senescence in PMM. The DMRs in promoter (478) and gene bodies (5718) were main enriched in GTPase regulator activity and signaling cascade mediated pathway. Integration analysis revealed methylation status within gene promoter (or gene body) and miRNA promoter have significant negative correlation with mRNA and miRNA expression, respectively. Which included numerous genes were closely related to distinct phenotypic traits between LDM and PMM. For instance, the hypermethylation and down-expression of HK-2 and PFKFB4 decreased the glycolytic potential in PMM. In addition, we validated the promoter hypomethylation and up-expression of miR-378 results in silencing the target gene expression and inducing promoted capillaries biosynthesis in PMM. Together, these results provide a thorough understanding of muscle metabolism and development from an genomic and epigenetic perspective.
2016-05-24 | GSE81759 | GEO
Project description:Objective: Athletes increasingly engage in repeated sprint training that consists of repeated short all-out effort interspersed by short periods of recovery. When performed in hypoxia (RSH), it may lead to greater training effects than in normoxia (RSN), however the underlying molecular mechanisms remain unclear. This study aimed at elucidating the effects of RSH on skeletal muscle oxidative and glycolytic adaptations as compared to RSN. Methods: Healthy young men performed nine repeated sprint training sessions in three weeks. Each training session consisted in six series of six sprints in either normoxia (FiO2 = 20.9%, RSN, n = 7) or normobaric hypoxia (FiO2 = 13.6%, RSH, n = 9). Before and after the training period, exercise performance was assessed by using repeated sprint ability (RSA) and Wingate tests. Vastus lateralis muscle biopsies were performed to investigate muscle metabolic adaptations using proteomic combined to western blotting analyses. Results: We observed similar improvements in RSA and Wingate tests in both RSH and RSN groups. Proteomic analysis revealed a decrease in several proteins involved in oxidative phosphorylation (OXPHOS) in both groups and this was confirmed with western blot showing significant reductions in complexes I and V protein levels. RSN and RSH increased protein levels of the glycolytic enzyme hexokinase II, while only RSH induced a significant increase in the glucose transporter 4 (GLUT4) protein levels, suggesting superior glycolytic adaptations in response to hypoxia. This phenotype is further supported by proteomics data showing significant increase of proteins involved in glycolysis. Our proteomics data showed in the RSH group a specific increase in several S100A family proteins, among which S100A13 was the most modified, a result confirmed by western blot. S100A proteins have recently been shown to accelerate glycolytic phenotype of cancer cells by activating the protein kinase B (Akt) pathway. Our data corroborate these findings by showing in RSH group increased Akt phosphorylation as well as increased levels of proteins related to Akt downstream effects such as enhanced translation. Conclusions: Altogether our data indicate that RSH, as compared to RSN, potentiates the muscle glycolytic phenotype, possibly through the activation of S100A13 and the Akt pathway.
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Project description:Metabolism is tightly coupled with the process of aging, and tumorigenesis. However, the mechanisms regulating metabolic properties in different contexts remain unclear. Cellular senescence is widely recognized as an important tumor suppressor function and accompanies metabolic remodeling characterized by increased mitochondrial oxidative phosphorylation (OXPHOS). Here we showed retinoblastoma (RB) is required for the increased OXPHOS in oncogene-induced senescent (OIS) cells. Combined metabolic and gene expression profiling revealed that RB mediated activation of the glycolytic pathway in OIS cells, causing upregulation of several glycolytic genes and concomitant increases in the levels of associated metabolites in the glycolytic pathway. Knockdown of these genes by small interfering RNAs (siRNAs) resulted in decreased mitochondrial respiration, suggesting that RB-mediated glycolytic gene activation promotes metabolic flux into the OXPHOS pathway. These results suggest that coordinate transcriptional activation of metabolic genes by RB enables OIS cells to maintain metabolically bivalent states that both glycolysis and OXPHOS are highly active. Collectively, our findings demonstrated a previously unrecognized function of RB in OIS cells. To understand the role of RB, we investigated the effect of RB1-knockdown in the transcription profile of oncogene-induced senescent (OIS) cells. IMR90 ER:Ras cells were treated with 100 nM 4-OHT for 6 days to induce senescence. RNA was isolated 6 days after OHT treatment and hybridized to Affymetrix microarrays. SiRNA transfection (control siRNA or siRB1) was performed 4 days before RNA isolation.
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Project description:The physiological, biochemical and functional difference of oxidative and glycolytic muscles play important roles in human metabolic health as well as in meat quality of animal. To explore this aspect, we firstly provided a genome-wide landscape of DNA methylomes and their relationship with mRNA and miRNA transcriptome for PMM (psoas major muscle; oxidative) and LDM (longissimus dorsi muscle; glycotic) in this study. We observed hypomethylation of subtelomeric regions and high mitochondria content contributed to fast replicative senescence in PMM. The DMRs in promoter (478) and gene bodies (5718) were main enriched in GTPase regulator activity and signaling cascade mediated pathway. Integration analysis revealed methylation status within gene promoter (or gene body) and miRNA promoter have significant negative correlation with mRNA and miRNA expression, respectively. Which included numerous genes were closely related to distinct phenotypic traits between LDM and PMM. For instance, the hypermethylation and down-expression of HK-2 and PFKFB4 decreased the glycolytic potential in PMM. In addition, we validated the promoter hypomethylation and up-expression of miR-378 results in silencing the target gene expression and inducing promoted capillaries biosynthesis in PMM. Together, these results provide a thorough understanding of muscle metabolism and development from an genomic and epigenetic perspective.
2016-05-24 | GSE81755 | GEO
Project description:The physiological, biochemical and functional difference of oxidative and glycolytic muscles play important roles in human metabolic health as well as in meat quality of animal. To explore this aspect, we firstly provided a genome-wide landscape of DNA methylomes and their relationship with mRNA and miRNA transcriptome for PMM (psoas major muscle; oxidative) and LDM (longissimus dorsi muscle; glycotic) in this study. We observed hypomethylation of subtelomeric regions and high mitochondria content contributed to fast replicative senescence in PMM. The DMRs in promoter (478) and gene bodies (5718) were main enriched in GTPase regulator activity and signaling cascade mediated pathway. Integration analysis revealed methylation status within gene promoter (or gene body) and miRNA promoter have significant negative correlation with mRNA and miRNA expression, respectively. Which included numerous genes were closely related to distinct phenotypic traits between LDM and PMM. For instance, the hypermethylation and down-expression of HK-2 and PFKFB4 decreased the glycolytic potential in PMM. In addition, we validated the promoter hypomethylation and up-expression of miR-378 results in silencing the target gene expression and inducing promoted capillaries biosynthesis in PMM. Together, these results provide a thorough understanding of muscle metabolism and development from an genomic and epigenetic perspective.
2016-05-24 | GSE81757 | GEO