Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure.

Détails

ID Serval
serval:BIB_46205B0D685E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure.
Périodique
Journal of the American Society of Nephrology
Auteur(s)
Letavernier E., Perez J., Joye E., Bellocq A., Fouqueray B., Haymann J.P., Heudes D., Wahli W., Desvergne B., Baud L.
ISSN
1046-6673
Statut éditorial
Publié
Date de publication
2005
Peer-reviewed
Oui
Volume
16
Numéro
8
Pages
2395-2402
Langue
anglais
Notes
Publication types: Journal Article
Résumé
Ischemic acute renal failure is characterized by damages to the proximal straight tubule in the outer medulla. Lesions include loss of polarity, shedding into the tubule lumen, and eventually necrotic or apoptotic death of epithelial cells. It was recently shown that peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) increases keratinocyte survival after an inflammatory reaction. Therefore, whether PPARbeta/delta could contribute also to the control of tubular epithelium death after renal ischemia/reperfusion was tested. It was found that PPARbeta/delta+/- and PPARbeta/delta-/- mutant mice exhibited much greater kidney dysfunction and injury than wild-type counterparts after a 30-min renal ischemia followed by a 36-h reperfusion. Conversely, wild-type mice that were given the specific PPARbeta/delta ligand L-165041 before renal ischemia were completely protected against renal dysfunction, as indicated by the lack of rise in serum creatinine and fractional excretion of Na+. This protective effect was accompanied by a significant reduction in medullary necrosis, apoptosis, and inflammation. On the basis of in vitro studies, PPARbeta/delta ligands seem to exert their role by activating the antiapoptotic Akt signaling pathway and, unexpectedly, by increasing the spreading of tubular epithelial cells, thus limiting potentially their shedding and anoikis. These results point to PPARbeta/delta as a remarkable new target for preconditioning strategies.
Mots-clé
Acetic Acids/pharmacology, Animals, Apoptosis, Blotting, Western, Cells, Cultured, Creatinine/blood, Dose-Response Relationship, Drug, Epithelial Cells/cytology, Humans, In Situ Nick-End Labeling, Inflammation, Ischemia, Keratinocytes/metabolism, Kidney/cytology, Kidney/metabolism, Kidney Failure/pathology, Kidney Tubules/metabolism, Ligands, Macrophages/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Fluorescence, Necrosis, Neutrophils/pathology, PPAR delta/biosynthesis, PPAR delta/physiology, PPAR-beta/biosynthesis, PPAR-beta/physiology, Peroxidase/metabolism, Phenols/pharmacology, Phenotype, Phenoxyacetates, Proto-Oncogene Proteins c-akt/metabolism, Signal Transduction, Sodium/chemistry, Time Factors
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 16:27
Dernière modification de la notice
08/05/2019 17:56
Données d'usage