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Updated: May 29, 2026

Modeling Hypoxia/Reoxygenation Injury in Proximal Tubular Epithelial Cells
06:23

Modeling Hypoxia/Reoxygenation Injury in Proximal Tubular Epithelial Cells

Published on: November 21, 2025

Role of Lipid Signaling by Platelet-Activating Factor Receptor in Tubular Epithelial Cells in Acute Kidney

Liangjing Lv1, Wang Xin, Qigang Lan

  • 1Department of Nephrology, the Key Laboratory for the Prevention and Treatment of Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Journal of the American Society of Nephrology : JASN
|May 27, 2026
PubMed
Abstract

Insights

Platelet activating factor receptor (PTAFR) drives kidney injury progression by causing cell cycle arrest in tubular cells. Inhibiting PTAFR may prevent acute kidney injury from becoming chronic kidney disease.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Pharmacology

Background:

  • Acute kidney injury (AKI) frequently progresses to chronic kidney disease (CKD) with limited treatment options.
  • G protein-coupled receptors (GPCRs) are implicated in various diseases and represent potential therapeutic targets.
  • The role of platelet activating factor receptor (PTAFR) in the AKI-to-CKD transition was investigated.

Purpose of the Study:

  • To elucidate the role of PTAFR in renal tubular epithelial cells (RTECs) during AKI.
  • To identify the mechanisms by which PTAFR contributes to AKI progression.
  • To explore PTAFR as a therapeutic target for preventing AKI-to-CKD transition.

Main Methods:

  • Utilized a mouse model of ischemia-reperfusion injury (IRI) induced AKI.
  • Investigated PTAFR function in tubule-specific Ptafr deficiency mice.
  • Employed transcriptomic profiling, flow cytometry, co-immunoprecipitation, western blotting, immunofluorescence, and lipidomic analysis.
  • Performed high-throughput virtual screening (HTVS) to identify PTAFR inhibitors.

Main Results:

  • PTAFR expression increased in RTECs post-AKI.
  • PTAFR deficiency attenuated RTEC injury and kidney fibrosis.
  • PTAFR induced RTEC G2/M arrest by inhibiting MDM2-mediated p53 degradation.
  • Identified phosphatidylethanolamine (PE) (18:0/18:1) as a novel PTAFR ligand.
  • Urinary PE (18:0/18:1) levels correlated with kidney dysfunction and distinguished AKI patients.
  • Identified WAY-639497 as a PTAFR antagonist mitigating AKI-induced injury and fibrosis.

Conclusions:

  • PTAFR promotes RTEC G2/M arrest via p53 pathway modulation, contributing to AKI-to-CKD progression.
  • PTAFR antagonism represents a potential therapeutic strategy for AKI.
  • Urinary PE (18:0/18:1) may serve as a biomarker for AKI.
Keywords:
AKICKDrenal tubular epithelial cells

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