biostudies-literatureChen YLife and Health Special Project of Hefei Science and Technology Bureau2023 Research Project of the Institute of Xin'an Medicine and Modernization of Traditional Chinese Medicine, Institute of Health Sciences, Hefei Comprehensive National Science Center2023 Research Project of the Institute of Xin'an Medicine and Modernization of Traditional Chinese Medicine, Institute of Health Sciences, Hefei Comprehensive National Science CenterNatural Science Foundation of Anhui ProvinceNational Natural Science Foundation of ChinaClinical Research Project of Anhui University of Chinese MedicineHealth Research Project of Anhui Provincial Health Commission121https://www.ebi.ac.uk/biostudies/studies/S-EPMC12932785biostudies-literatureUnknown83(1)Glycolytic reprogramming is closely associated with chronic kidney disease (CKD) progression. However, the role and mechanism of phosphofructokinase muscle type (PFKM), a core rate-limiting enzyme in glycolysis, in renal fibrosis remain unclear. This study analyzed Gene Expression Omnibus (GEO) datasets of renal tissues from patients with CKD to construct a folic acid (FA)-induced mouse model of renal fibrosis. PFKM overexpression or knockdown was achieved specifically in renal tubular epithelial cells using an adeno-associated virus serotype 9 (AAV9) vector. Additionally, combined with a transforming growth factor-β1 (TGF-β1)-stimulated human kidney-2 (HK-2) cell model, the underlying mechanism was explored via histological staining, metabolic analysis, ribonucleic acid (RNA) sequencing (Cellular and molecular life sciences : CMLSThe glycolytic enzyme PFKM promotes renal fibrosis by activating the NF-κB pathway via lactate-mediated H3K18 lactylation.PMC129327852023CXMMTCM018AHWJ2024BAc20084, AHWJ2024Aa30409GJ2022SM032308085MH292, 2408085QH2822024YFYLCZX2882274307Zhang WDai RGao YChen YWang WCheng MZhang LSang YWang YWei LfalseThe glycolytic enzyme PFKM promotes renal fibrosis by activating the NF-κB pathway via lactate-mediated H3K18 lactylation.Glycolytic reprogramming is closely associated with chronic kidney disease (CKD) progression. However, the role and mechanism of phosphofructokinase muscle type (PFKM), a core rate-limiting enzyme in glycolysis, in renal fibrosis remain unclear. This study analyzed Gene Expression Omnibus (GEO) datasets of renal tissues from patients with CKD to construct a folic acid (FA)-induced mouse model of renal fibrosis. PFKM overexpression or knockdown was achieved specifically in renal tubular epithelial cells using an adeno-associated virus serotype 9 (AAV9) vector. Additionally, combined with a transforming growth factor-β1 (TGF-β1)-stimulated human kidney-2 (HK-2) cell model, the underlying mechanism was explored via histological staining, metabolic analysis, ribonucleic acid (RNA) sequencing (2026-01-01T00:00:00Z2026 Feb2026-07-16T21:39:27.578Z2026-07-10T03:15:12.869ZS-EPMC129327854171188810.1007/s00018-026-06118-z