In diabetic nephropathy, knocking out sirtuin 3 can induce TGF-β/smad3 signaling, which increases the accumulation of HIF-1α and formation of PKM2 dimers, and enhances the transcription of glycolytic enzymes, leading to the accumulation of glycolytic intermediates before pyruvate, induces abnormal glycolysis, and helps to drive EMT, thus accelerating renal fibrosis (97). The gene discussed is SMAD3; the disease is renal fibrosis.