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

Chen,Lei; Bai,Jun; Li,Yanfei

doi:10.3892/mmr.2020.11164

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

Authors:
- Lei Chen
- Jun Bai
- Yanfei Li
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Affiliations: Department of Physical Education, Shanghai Jiaotong University, Shanghai 200240, P.R. China, Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China, Office of Academic Research, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, P.R. China
Published online on: May 20, 2020 https://doi.org/10.3892/mmr.2020.11164
Pages: 661-670
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 α1 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.

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