BACKGROUND AND PURPOSEPeroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, and three subtypes (a, b and g) 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.
EXPERIMENTAL APPROACHBy 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.
KEY RESULTSOnly 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.
CONCLUSION AND IMPLICATIONSThese findings contribute to clarification of the pathophysiological role of renal PPARs and suggest that selective PPARa, PPARb or PPARg agonists may exert similar protective effects on podocytes by decreasing apoptotic cell death.
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