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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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KLF6 enhances ferroptosis in S-AKI through the NCOA4/ACSL4/LPCAT3 axis

You Zhou1, You Wu2, Rui Zhu1

  • 1Intensive Care Unit, Beijing Anzhen Nanchong Hospital of Capital Medical University & Nanchong Central Hospital, Nanchong, Sichuan, China; The Second Clinical Medical College of North Sichuan Medical College, Nanchong, Sichuan, China.

International Immunopharmacology
|August 14, 2025
PubMed
Abstract

Insights

Transcription factor KLF6 promotes septic acute kidney injury (S-AKI) by increasing ferroptosis. Inhibiting KLF6 reduces kidney damage and ferroptosis in S-AKI models, offering a potential therapeutic target.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cellular Pathology

Background:

  • Septic acute kidney injury (S-AKI) is a significant clinical challenge with no effective treatments.
  • The precise role of Krüppel-like factor 6 (KLF6) in S-AKI pathogenesis remains unclear.

Purpose of the Study:

  • To elucidate the role of KLF6 in the development and progression of S-AKI.
  • To investigate KLF6's regulatory mechanisms and its impact on ferroptosis in S-AKI.

Main Methods:

  • Utilized mouse cecal ligation and puncture (CLP) model and in vitro systems to study KLF6.
  • Employed ChIP-qPCR, luciferase assays, and biochemical methods to analyze KLF6 targets and cellular damage.
  • Assessed ferroptosis using transmission electron microscopy (TEM) and lipid peroxidation markers.

Main Results:

  • KLF6 expression was elevated in S-AKI models.
  • KLF6 knockdown ameliorated kidney injury and reduced ferroptosis, while overexpression worsened these effects.
  • KLF6 directly regulates Nuclear Receptor Coactivator 4 (NCOA4) transcription, a key mediator of ferroptosis.

Conclusions:

  • KLF6 plays a critical role in exacerbating S-AKI by promoting ferroptosis.
  • KLF6-induced NCOA4 transcription is a key mechanism driving ferroptosis in S-AKI.
  • Targeting KLF6 presents a promising therapeutic strategy for S-AKI.
Keywords:
FerroptosisKLF6NCOA4S-AKITargeted therapy

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