biostudies-literatureCai XGuangzhou Municipal Science and Technology ProjectNational Natural Science Foundation of ChinaNatural Science Foundation of Guangdong Province159https://www.ebi.ac.uk/biostudies/studies/S-EPMC12003256biostudies-literatureUnknown82(1)<h4>Background and objective</h4>Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to prevent the progression of diabetic kidney disease (DKD). However, their impact on renal fibrosis remains largely uninvestigated. This study aimed to explore the effect of SGLT2 inhibitor empagliflozin on renal fibrosis in DKD patients and DKD models, and the molecular mechanisms involved.<h4>Methods</h4>Kidney samples of DKD patients and DKD models were used in this study. DKD mouse models included STZ-treated CD-1 mice and HFD-fed C57BL/6 mice were all treated with empagliflozin for 6 to 12 weeks. Kidney pathological changes were analysed and fibrotic factors were detected. HK-2 cells were treated with normal glucose (NG), high glucose (HG), or HG with empagliflozin. RNA sequencing was eCellular and molecular life sciences : CMLSSGLT2 inhibitor empagliflozin ameliorates tubulointerstitial fibrosis in DKD by downregulating renal tubular PKM2.PMC120032562017070101182020A1515011245816707622016A03031325882270942Wang MCao HLiang XLiang HCai MYu PXu FCai XfalseSGLT2 inhibitor empagliflozin ameliorates tubulointerstitial fibrosis in DKD by downregulating renal tubular PKM2.<h4>Background and objective</h4>Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to prevent the progression of diabetic kidney disease (DKD). However, their impact on renal fibrosis remains largely uninvestigated. This study aimed to explore the effect of SGLT2 inhibitor empagliflozin on renal fibrosis in DKD patients and DKD models, and the molecular mechanisms involved.<h4>Methods</h4>Kidney samples of DKD patients and DKD models were used in this study. DKD mouse models included STZ-treated CD-1 mice and HFD-fed C57BL/6 mice were all treated with empagliflozin for 6 to 12 weeks. Kidney pathological changes were analysed and fibrotic factors were detected. HK-2 cells were treated with normal glucose (NG), high glucose (HG), or HG with empagliflozin. RNA sequencing was e2025-01-01T00:00:00Z2025 Apr2025-07-12T03:04:24.998Z2025-07-12T03:04:24.998ZS-EPMC120032564023785410.1007/s00018-025-05688-8