Skeletal muscle expression profile changes in early stages of sepsis.
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ABSTRACT:
PROVIDER: PRJNA1047542 | ENA |
REPOSITORIES: ENA
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Project description:Sepsis-induced skeletal muscle atrophy is common in septic patients with the increases risk of mortality and is associated with myocellular mitochondrial dysfunction. Nevertheless, the specific mechanism of sepsis muscle atrophy remains unclear. Here we conducted a clinical retrospective analysis and observed the elevation of skeletal muscle index (ΔSMI) was an independent risk factor for 60-day mortality in septic patients. Moreover, in mouse model of sepsis, the skeletal muscle atrophy was also observed, which was associated with the upregulation of S100a8/a9-mediated mitochondrial dysfunction. Inhibition of S100a8/a9 significantly improved mitochondrial function and alleviated muscle atrophy. Conversely, administration of recombinant S100a8/a9 protein exacerbated mitochondrial energy exhaustion and myocyte atrophy. Mechanistically, S100a8/a9 binding to RAGE induced Drp1 phosphorylation and mitochondrial fragmentation, resulting in muscle atrophy. Additionally, RAGE ablation or administration of Drp1 inhibitor significantly reduced Drp1-mediated mitochondrial fission, improved mitochondrial morphology and function. Our findings indicated the pivotal role of S100a8/a9 in driving the mitochondrial fragmentation in septic muscle atrophy. Targeting S100a8/a9-RAGE-initiated mitochondrial fission might offer a promising therapeutic intervention against septic muscle atrophy. Taken together, our data provide a potential mechanism for sepsis-induced muscle atrophy.
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Project description:We generated 364.63 Gb of high-quality bulk RNA sequencing data from the skeletal muscle samples (approximately 6.75 Gb per sample). This dataset provided insightful gene expression information to understand the role of ZBED6 gene on skeletal muscle atrophy in sepsis. In addition, this dataset can be used for heterogeneity analysis between skeletal muscle tissues from multiple species or female pigs.
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Project description:Texel and Ujumqin sheep show obvious differences in muscle and fat growth, so they are ideal models not only to understand the molecular mechanism in prenatal skeletal muscle development, but to identify the potential target genes of myostatin. To elucidate the phenotypic variation between the two sheep breeds and the dynamic characteristics of gene expression in skeletal muscle during the development, we examined the development of skeletal muscle in transcriptome-wide level at 70, 85,100,120 , 135 days post coitus (dpc),birth, 1 month and 2 month. Using the specialized and standardized sheep transcriptome-wide oligo DNA microarray (Agilent), we analyzed the transcriptomic profiles of longissmuss dorsi muscle from fetuses of Texel and Ujumqin sheep. We characterized dynamic transcriptome-wide profiles that accompany the prenatal skeletal muscle and fat development in Texel and Ujumqin sheep respectively, and compared the difference in profiles of gene expression between the two sheep breeds at the same developmental stage.Some potential myostatin target genes and other genes controlling the growth of skeletal muscle and adipose were identified for further examinations. Our findings not only contribute to understand the molecular mechanism of prenatal skeletal muscle development in large precocial species, but also provide some clues for human myopathy and obesity at prenatal stages. Moreover, we also can identify putative candidate genes for meat quality traits in farm animals. Longissimus dorsi muscles were sampled from five prenatal development stages (70, 85, 100, 120 and 135 day of gestation) in Texel and eight development stages (at 70, 85, 100, 120, 135 days post coitus (dpc), birth, 1 month and 2 month) in Ujumqin sheep. There were at least three replicates at each development time in each breed. Two gene expression experiments were conducted with a total of 40 hybridizations.
2010-12-20 | E-GEOD-23563 | biostudies-arrayexpress
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2020-09-01 | GSE157043 | GEO
Project description:Texel and Ujumqin sheep show obvious differences in muscle and fat growth, so they are ideal models not only to understand the molecular mechanism in prenatal skeletal muscle development, but to identify the potential target genes of myostatin. To elucidate the phenotypic variation between the two sheep breeds and the dynamic characteristics of gene expression in skeletal muscle during the development, we examined the development of skeletal muscle in transcriptome-wide level at 70, 85,100,120 , 135 days post coitus (dpc),birth, 1 month and 2 month. Using the specialized and standardized sheep transcriptome-wide oligo DNA microarray (Agilent), we analyzed the transcriptomic profiles of longissmuss dorsi muscle from fetuses of Texel and Ujumqin sheep. We characterized dynamic transcriptome-wide profiles that accompany the prenatal skeletal muscle and fat development in Texel and Ujumqin sheep respectively, and compared the difference in profiles of gene expression between the two sheep breeds at the same developmental stage.Some potential myostatin target genes and other genes controlling the growth of skeletal muscle and adipose were identified for further examinations. Our findings not only contribute to understand the molecular mechanism of prenatal skeletal muscle development in large precocial species, but also provide some clues for human myopathy and obesity at prenatal stages. Moreover, we also can identify putative candidate genes for meat quality traits in farm animals.
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