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Updated: May 25, 2026

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics
12:28

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics

Published on: January 11, 2019

DR3 signaling protects against cisplatin nephrotoxicity mediated by tumor necrosis factor

Rafia S Al-Lamki1, WanHua Lu, Sarah Finlay

  • 1Department of Medicine, Biomedical Research Center, Addenbrooke's Hospital, Cambridge, United Kingdom. rsma2@hermes.cam.ac.uk

The American Journal of Pathology
|February 15, 2012
PubMed

Insights

Activating death receptor 3 (DR3) signaling mitigates cisplatin-induced nephrotoxicity by antagonizing tumor necrosis factor (TNF)-induced apoptosis. This suggests DR3 activation may protect against acute kidney injury.

Area of Science:

  • Nephrology
  • Immunology
  • Cell Biology

Background:

  • Death receptor 3 (DR3) expression increases in human tubular epithelial cells (TECs) during renal injury.
  • The specific role of DR3 in renal injury is not well understood.

Purpose of the Study:

  • To investigate the in vivo function of DR3 in cisplatin-induced kidney injury.
  • To determine if DR3 signaling influences TEC apoptosis and inflammation.

Main Methods:

  • Utilized wild-type (DR3(+/+)) and DR3-deficient (DR3(-/-)) mice treated with cisplatin.
  • Examined DR3, TNF-like ligand 1A (TL1A), and TNF expression in TECs.
  • Assessed TEC apoptosis and NF-κB activation.
  • Used mouse kidney organ cultures and a proximal tubule cell line (TKPTS).

Main Results:

  • Cisplatin induced DR3, TL1A, and TNF expression in TECs.
  • DR3 deficiency exacerbated cisplatin-induced TEC apoptosis.
  • DR3 signaling reduced phospho-NF-κBp65(Ser276) levels, indicating reduced inflammation.
  • TNF inhibition lessened tubular damage, while TL1A reduced cisplatin-induced apoptosis in DR3(+/+) TECs.

Conclusions:

  • DR3 signaling mitigates cisplatin-induced nephrotoxicity.
  • DR3 activation may counteract TNF-mediated pro-apoptotic signals in TECs.
  • Activating DR3 could be a therapeutic strategy for acute kidney injury.

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