The subtypes of peroxisome proliferator-activated receptors expressed by human podocytes and their role in decreasing podocyte injury.
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.
Miglio
Gianluca
G
Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Turin, Italy. gianluca.miglio@unito.it
Rosa
Arianna Carolina
AC
Rattazzi
Lorenza
L
Grange
Cristina
C
Collino
Massimo
M
Camussi
Giovanni
G
Fantozzi
Roberto
R
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
D016895:Culture Media, Serum-Free; D047492:Peroxisome Proliferator-Activated Receptors; D053148:Caspase 3