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c-Jun-N-Terminal Kinase Signaling Is Involved in Cyclosporine-Induced Epithelial Phenotypic Changes

Nicolas Pallet1, Eric Thervet, Dany Anglicheau

  • 1Unité INSERM U775, Centre Universitaire des Saints-Pères, Université Paris Descartes, 75006 Paris, France.

Journal of Transplantation
|October 27, 2011
PubMed

Insights

Cyclosporine A (CsA) triggers kidney tubule cell changes via endoplasmic reticulum (ER) stress and c-jun-N-terminal kinase (JNK) signaling. Inhibiting JNK reduces these CsA-induced effects, suggesting JNK

Area of Science:

  • Nephrology
  • Cell Biology
  • Toxicology

Background:

  • Tubular epithelial cells are crucial in chronic kidney disease pathogenesis.
  • Cyclosporine A (CsA) induces epithelial phenotypic changes (EPCs) resembling incomplete epithelial to mesenchymal transition (EMT) independently of TGF-β.
  • Endoplasmic reticulum (ER) stress is implicated in CsA-induced tubular cell plasticity.

Purpose of the Study:

  • To investigate the role of c-jun-N-terminal kinase (JNK) signaling in CsA-induced EPCs.
  • To determine if JNK activation mediates CsA's effects on tubular epithelial cells.

Main Methods:

  • Primary cultures of human renal epithelial cells were used.
  • Cells were exposed to CsA.
  • JNK signaling activation and the effects of a JNK inhibitor were assessed.

Main Results:

  • CsA activated JNK signaling in human renal epithelial cells.
  • JNK inhibition decreased CsA-induced cell shape changes, E-cadherin downregulation, migration, and Snail-1 expression.
  • Results suggest JNK signaling mediates CsA-induced morphological alterations via Snail-1 regulation.

Conclusions:

  • CsA-induced JNK activation plays a significant role in tubular epithelial cell plasticity.
  • Targeting JNK signaling may offer a therapeutic strategy for CsA-induced nephrotoxicity.
  • JNK pathway modulation is a key mechanism in CsA-induced kidney damage.

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