c-jun-n-terminal kinase signaling is involved in cyclosporine-induced epithelial phenotypic changesc-jun-n-terminal激酶信号参与cyclosporine-induced上皮表型变化.pdfVIP

Hindawi Publishing Corporation Journal of Transplantation Volume 2012, Article ID 348604, 6 pages doi:10.1155/2012/348604 Research Article c-Jun-N-Terminal Kinase Signaling Is Involved in Cyclosporine-Induced Epithelial Phenotypic Changes Nicolas Pallet,1 Eric Thervet,1, 2 and Dany Anglicheau1, 3 1 Unite INSERM U775, Centre Universitaire des Saints-Peres, Universite Paris Descartes, 75006 Paris, France ´ ` ´ 2 Service de Nephrologie, Hopital Europeen Georges Pompidou, 75015 Paris, France ´ ˆ ´ 3 Service de Transplantation Renale, Hopital Necker, Universite Paris Descartes, 75006 Paris, France ´ ˆ ´ Correspondence should be addressed to Nicolas Pallet, npallet@yahoo.fr Received 24 May 2011; Accepted 15 August 2011 Academic Editor: Bruce Kaplan Copyright © 2012 Nicolas Pallet et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Tubular epithelial cells play a central role in the pathogenesis of chronic nephropathies. Previous toxicogenomic studies have demonstrated that cyclosporine- (CsA-) induced epithelial phenotypic changes (EPCs) are reminiscent of an incomplete epithelial to mesenchymal transition (EMT) in a TGF-β -independent manner. Furthermore, we identified endoplasmic reticulum (ER) stress as a potential mechanism that may participate in the modulation of tubular cell plasticity during CsA exposure. Because c-jun-N- terminal kinase (JNK), which is activated during ER stress, is implicated in kidney fibrogenesis, we unde