Dataset Information

MiR?29 mediates exercise?induced skeletal muscle angiogenesis by targeting VEGFA, COL4A1 and COL4A2 via the PI3K/Akt signaling pathway.

ABSTRACT: The present study investigated the molecular changes and related regulatory mechanisms in the response of skeletal muscle to exercise. The microarray dataset 'GSE109657' of the skeletal muscle response to high?intensity intermittent exercise training (HIIT) was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened and analyzed using weighted gene co?expression network analysis (WGCNA) to identify the significant functional co?expressed gene modules. Moreover, functional enrichment analysis was performed for the DEGs in the significant modules. In addition, protein?protein interaction (PPI) network and microRNA (miR)?transcription factor (TF)?target regulatory network were constructed. A total of 530 DEGs in the skeletal muscle were screened after HIIT, suggesting an effect of HIIT on the skeletal muscle. Moreover, three significant modules (brown, blue and red modules) were identified after WGCNA, and the genes Collagen Type IV ?1 Chain (COL4A1) and COL4A2 in the brown module showed the strongest correlation with HIIT. The DEGs in the three modules were significantly enriched in focal adhesion, extracellular matrix organization and the PI3K/Akt signaling pathway. Furthermore, the PPI network contained 104 nodes and 211 interactions. Vascular endothelial growth factor A (VEGFA), COL4A1 and COL4A2 were the hub genes in the PPI network, and were all regulated by miR?29a/b/c. In addition, VEGFA, COL4A1 and COL4A2 were significantly upregulated in the skeletal muscle response to HIIT. Therefore, the present results suggested that the growth and migration of vascular endothelial cells, and skeletal muscle angiogenesis may be regulated by miR?29a/b/c targeting VEGFA, COL4A1 and COL4A2 via the PI3K/Akt signaling pathway. The present results may provide a theoretical basis to investigate the effect of exercise on skeletal muscle.

SUBMITTER: Chen L

PROVIDER: S-EPMC7339600 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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miR‑29 mediates exercise‑induced skeletal muscle angiogenesis by targeting VEGFA, COL4A1 and COL4A2 via the PI3K/Akt signaling pathway.

Chen Lei L Bai Jun J Li Yanfei Y

Molecular medicine reports 20200520 2

The present study investigated the molecular changes and related regulatory mechanisms in the response of skeletal muscle to exercise. The microarray dataset 'GSE109657' of the skeletal muscle response to high‑intensity intermittent exercise training (HIIT) was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened and analyzed using weighted gene co‑expression network analysis (WGCNA) to identify the significant functional co‑expressed gene mod ...[more]

PMID: 32467996

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Project description:Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD risk.

Dataset Information

MiR?29 mediates exercise?induced skeletal muscle angiogenesis by targeting VEGFA, COL4A1 and COL4A2 via the PI3K/Akt signaling pathway.

Publications

miR‑29 mediates exercise‑induced skeletal muscle angiogenesis by targeting VEGFA, COL4A1 and COL4A2 via the PI3K/Akt signaling pathway.

Similar Datasets

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