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High-dose Pyruvate Treatment Alters Skeletal Muscle Differentiation And Expression Of Inflammation-related Genes

Kazuya Hasegawa, Yuya Yamaguchi, Yutthana Pengjam

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ABSTRACTPyruvic acid therapy is used for various diseases, but the therapeutic effect decreases at high doses. The molecular mechanism of high-dose pyruvate is not well understood. The purpose of this study was to identify the effects of high dose pyruvate addition on skeletal muscle using C2C12. The gene expression profile for the GSE5497 dataset was taken from the Gene Expression Omnibus database. GEO2R was used to identify specifically expressed genes (DEGs). Functional analysis and pathway enrichment analysis of DEG were performed using the DAVID database. The protein-protein interaction (PPI) network was built in the STRING database and visualized using Cytoscape. GO analysis showed that up-regulated DEG was primarily involved in angiogenesis, cell adhesion, and inflammatory response. We also showed that down-regulated DEG is involved in the regulation of muscle contraction, skeletal muscle fiber development. In addition, the upregulated KEGG pathway of DEG included Rheumatoid arthritis, Chemokine signaling pathway, and Cytokine-cytokine receptor interaction. Downregulated DEG included Calcium signaling pathway, hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy, Neuroactive ligand-receptor interaction, and Cardiac muscle contraction. Further, analysis of two modules selected from the PPI network showed that high-dose pyruvate exposure to C2C12 was primarily associated with muscle contraction, muscle organ morphogenesis, leukocyte chemotaxis, and chemokine activity. In conclusion, High-dose pyruvate treatment of C2C12 was found to be associated with an increased inflammatory response and decreased skeletal muscle formation. However, further studies are still needed to verify the function of these molecules at high doses of pyruvate.