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Updated: Aug 25, 2025

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

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PFKFB3 mediates tubular cell death in cisplatin nephrotoxicity by activating CDK4

Lu Wen1, Qingqing Wei2, Man J Livingston2

  • 1Department of Nephrology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, China; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, Georgia, USA.

Translational Research : the Journal of Laboratory and Clinical Medicine
|October 15, 2022
PubMed

Insights

Cisplatin cancer drug causes kidney damage. Researchers found that inhibiting 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) protected kidney cells by blocking the CDK4/Rb pathway, offering a new kidney protection strategy.

Area of Science:

  • Nephrology
  • Oncology
  • Molecular Biology

Background:

  • Cisplatin is a vital chemotherapy agent but causes significant nephrotoxicity.
  • The precise mechanisms underlying cisplatin-induced kidney damage are not fully understood.
  • Currently, no effective strategies exist to prevent cisplatin nephrotoxicity.

Purpose of the Study:

  • To elucidate the role of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in cisplatin nephrotoxicity.
  • To investigate PFKFB3's novel nuclear function in kidney tubular cells.
  • To explore PFKFB3 as a potential therapeutic target for preventing kidney damage during cisplatin treatment.

Main Methods:

  • Investigated PFKFB3 expression in vitro and in vivo cisplatin nephrotoxicity models.
  • Utilized pharmacological inhibition and genetic silencing of PFKFB3.
  • Examined the interaction between PFKFB3 and cyclin-dependent kinase 4 (CDK4) using mouse models.
  • Assessed the impact of PFKFB3 inhibition on apoptosis and kidney injury.

Main Results:

  • PFKFB3 expression was induced in kidney tubular cells during cisplatin treatment.
  • PFKFB3 inhibition or silencing reduced cisplatin-induced apoptosis in renal proximal tubular cells (RPTCs).
  • Knockout of PFKFB3 in RPTCs ameliorated cisplatin-induced kidney injury.
  • PFKFB3 interacted with CDK4, leading to CDK4 activation and retinoblastoma tumor suppressor (Rb) inactivation.

Conclusions:

  • PFKFB3 plays a critical role in cisplatin nephrotoxicity via the CDK4/Rb pathway.
  • Targeting PFKFB3 offers a promising strategy for kidney protection in cancer patients receiving cisplatin.
  • This study reveals a novel mechanism of PFKFB3 in kidney tubular cells and a potential therapeutic avenue.

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