Premium
The subtypes of peroxisome proliferator‐activated receptors expressed by human podocytes and their role in decreasing podocyte injury
Author(s) -
Miglio Gianluca,
Rosa Arianna Carolina,
Rattazzi Lorenza,
Grange Cristina,
Collino Massimo,
Camussi Giovanni,
Fantozzi Roberto
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.01032.x
Subject(s) - podocyte , rosiglitazone , peroxisome proliferator activated receptor , ppar agonist , receptor , nephrin , agonist , medicine , apoptosis , programmed cell death , endocrinology , pioglitazone , biology , chemistry , kidney , diabetes mellitus , type 2 diabetes , biochemistry , proteinuria
BACKGROUND AND PURPOSE 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. EXPERIMENTAL APPROACH 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. KEY 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. CONCLUSION AND IMPLICATIONS 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.