title: The subtypes of peroxisome proliferator-activated receptors expressed by human podocytes and their role in decreasing podocyte injury.
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, and three subtypes (α, β and γ) have been identified. PPAR activation has been reported to decrease renal injury and markers of glomerular dysfunction in models of renal ischemia/reperfusion (I/R). However, both the I/R effects and the effects of PPAR agonists on podocytes, an integral cellular part of the glomerular filtration barrier, remain to be established.
  
  
  METHODS
  By using oxygen/glucose deprivation-reoxygenation as an in vitro model that mimics in vivo I/R, the effects of PPAR agonists on podocyte death were compared. Human immortalized podocytes were treated with gemfibrozil, GW0742, pioglitazone or rosiglitazone, as a single or repeated challenge. Cell loss, necrotic and apoptotic cell death were measured.
  
  
  RESULTS
  Only the repeated treatment with each PPAR agonist significantly prevented cell death, mainly by decreasing apoptosis. In comparison, in a model of serum deprivation-induced apoptosis, both treatments were effective, although the repeated treatment achieved the more pronounced effect. Finally, our results showed that preservation of Bcl-2, Bax and nephrin expression accompanied the anti-apoptotic effects exerted by PPAR agonists in human podocytes.
  
  
  CONCLUSIONS
  These findings contribute to clarification of the pathophysiological role of renal PPARs and suggest that selective PPARα, PPARβ or PPARγ agonists may exert similar protective effects on podocytes by decreasing apoptotic cell death.
authors.affiliation: Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Turin, Italy. gianluca.miglio@unito.it
authors.forename: Gianluca
authors.initials: G
authors.lastname: Miglio
authors.forename: Arianna Carolina
authors.initials: AC
authors.lastname: Rosa
authors.forename: Lorenza
authors.initials: L
authors.lastname: Rattazzi
authors.forename: Cristina
authors.initials: C
authors.lastname: Grange
authors.forename: Massimo
authors.initials: M
authors.lastname: Collino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
authors.forename: Roberto
authors.initials: R
authors.lastname: Fantozzi
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation; D006801:Humans; D018613:Microscopy, Confocal; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000145:classification* / Q000378:metabolism* / Q000502:physiology; D050199:Podocytes / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D016895:Culture Media, Serum-Free; D047492:Peroxisome Proliferator-Activated Receptors; D053148:Caspase 3