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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.

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