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Updated: May 10, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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Paliperidone Inhibits Ferroptosis Mediated by Autophagy in Renal Tubular Epithelial Cells by Targeting CHAC1

Xiangrong Ying1, Ke Gao1, Zhengang Luo1

  • 1Department of Urology, Shaoxing People's Hospital, Shaoxing, 312000, China.

Advanced Biology
|April 22, 2025
PubMed

Insights

This study reveals that CHAC1 gene upregulation contributes to kidney stone formation by promoting autophagy-mediated ferroptosis in renal tubular cells. The drug Paliperidone targets CHAC1, inhibiting this process and offering a new kidney stone treatment strategy.

Area of Science:

  • Nephrology
  • Cell Biology
  • Biochemistry

Background:

  • Renal tubular epithelial cell injury is a key factor in kidney stone development.
  • The role of autophagy-mediated ferroptosis in this injury is not well understood.

Purpose of the Study:

  • To investigate the role of CHAC1 in kidney stone formation.
  • To explore the therapeutic potential of Paliperidone in inhibiting autophagy-mediated ferroptosis.

Main Methods:

  • Bioinformatic analysis to identify ferroptosis-related genes.
  • In vitro cell models (HK-2 cells) treated with calcium oxalate (CaOx).
  • CHAC1 gene knockdown via shRNA, protein expression analysis (Western Blot), autophagy and ferroptosis marker detection, molecular docking, and cell thermal migration assays.

Main Results:

  • CHAC1 was found to be upregulated in kidney stones and linked to ferroptosis.
  • CHAC1 knockdown reduced CaOx-induced autophagy and ferroptosis.
  • Paliperidone (Pali) was shown to target CHAC1, inhibit its activity, and reduce autophagy-mediated ferroptosis.

Conclusions:

  • CHAC1 upregulation is associated with kidney stone formation via autophagy-mediated ferroptosis.
  • Paliperidone effectively inhibits this pathway by targeting CHAC1.
  • Targeting CHAC1 offers a novel therapeutic approach for kidney stone treatment.
Keywords:
CHAC1Paliperidoneautophagyferroptosisrenal tubular epithelial cells

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