Enhanced glycolysis in the process of renal fibrosis aggravated the development of chronic kidney disease

X.-N. Yin, J. Wang, L.-F. Cui, W.-X. Fan

Department of Nephrology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China. fanwx1999@163.com

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• Nephrology

OBJECTIVE: To explore the effect of glycometabolism on renal fibrosis and its underlying mechanism.

MATERIALS AND METHODS: For in vivo experiments, unilateral ureteral obstruction (UUO) mouse model was constructed to induce renal interstitial fibrosis. Fibrosis and proliferation indicators in renal tissues were detected to observe the fibroblast phenotype changes during the process of renal fibrosis. Moreover, mRNA and protein levels of key enzymes in glycometabolism were also detected. For in vitro experiments, plasmid transfection was performed to overexpress pyruvate kinase M2 (PKM2) to explore the relationship between PKM2 and renal interstitial fibrosis. Energy metabolism monitoring was performed to detect changes in aerobic glycolysis and oxidative phosphorylation during the process of TGF-β1-induced fibroblast phenotype changes.

RESULTS: Fibroblast phenotype was changed. Both fibrosis and proliferation indicators were upregulated during renal fibrosis. Meanwhile, elevated expressions of key enzymes in glycometabolism and metabolic reprogramming of fibroblasts were observed. Overexpressed PKM2 activated fibroblasts and induced renal interstitial fibrosis, accompanied by increased glycometabolism level.

CONCLUSIONS: Metabolic reprogramming promoted renal interstitial fibrosis, which leads to alteration of cell energy metabolism model.

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