The glycolytic enzyme PFKFB3 drives kidney fibrosis through promoting histone lactylation-mediated NF-κB family activation

Persistently elevated glycolysis in kidney has been demonstrated to promote chronic kidney disease (CKD). However, the underlying mechanism remains largely unclear. Here, we observed that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key glycolytic enzyme, was remarkably induced in kidney proximal tubular cells (PTCs) following ischemia-reperfusion injury (IRI) in mice, as well as in multiple etiologies of patients with CKD. PFKFB3 expression was positively correlated with the severity of kidney fibrosis. Moreover, patients with CKD and mice exhibited increased urinary lactate/creatine levels and kidney lactate, respectively. PTC-specific deletion of PFKFB3 significantly reduced kidney…

• NN
  National Natural Science Foundation of China

  Awards: 82070698, 81870464, 82270716, 82000640
• CP
  China Postdoctoral Science Foundation

  Award: 2018M640873
• NS
  Natural Science Foundation of Guangdong Province

  Awards: 2023A1515012477, 2017A050503003, 2020B1212060028
• GM
  Guangzhou Municipal Science and Technology Project