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Kidney Week

Abstract: PO0366

Inhibition of PFKFB3 Alleviates Cisplatin-Induced AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Wen, Lu, Central South University, Changsha, Hunan, China
  • Wei, Qingqing, Augusta University Department of Cellular Biology and Anatomy, Augusta, Georgia, United States
  • Dong, Zheng, Augusta University Department of Cellular Biology and Anatomy, Augusta, Georgia, United States

Metabolism and its reprogramming may have influence on acute kidney injury (AKI) and subsequent kidney repair. 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is an important rate-limiting enzyme in glycolysis. Recently, PFKFB3 has gained substantial interest as an attractive target for cancers and pulmonary hypertension therapy. However, the role of PFKFB3 in AKI remains poorly understood.


To investigate the role of PFKFB3 in cisplatin nephrotoxic AKI, we established stable PFKFB3 knockdown rat renal tubular cell lines (RPTC) and generated the kidney proximal tubule-specific PFKFB3 knock-out mice by crossing PFKFB3-floxed mice with PEPCK-CRE mice. PFKFB3-knockdown and wild-type RPTC cells were treated with 20μM cisplatin for 24h in vitro, while PFKFB3 knock-out or wild type male mice of 8-10 weeks were intraperitoneally injected with 30 mg/kg of cisplatin in vivo.


PFKFB3 was up-regulated in cisplatin-induced AKI models both in vitro and in vivo. In the mouse model, deficiency of PFKFB3 reduced cisplatin-induced kidney injury and improved renal functions. Moreover, genetic and pharmacological inhibition of PFKFB3 in RPTC cells suppressed cisplatin-induced apoptosis. In addition, phosphorylated Erk1/2, phosphorylated p38 and phosphorylated NF-κB were decreased in PFKFB3 knockdown RPTC cells compared to the vector group.


These results indicate that PFKFB3 is a key mediator of renal tubular injury in cisplatin-induced AKI and may be an effective therapeutic target for alleviating cisplatin nephrotoxicity in chemotherapy.


  • NIDDK Support