PPAR-gamma agonist protects podocytes from injury.

Kanjanabuch T, Ma LJ, Chen J, Pozzi A, Guan Y, Mundel P, Fogo AB
Kidney Int. 2007 71 (12): 1232-9

PMID: 17457378 · DOI:10.1038/sj.ki.5002248

Podocyte injury and loss contribute to progressive glomerulosclerosis. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear hormone receptor, which we have found to be increased in podocytes in a variety of kidney diseases. It is not known if PPAR-gamma contributes to renal injury or if it serves as a countermeasure to limit renal injury during disease progression. We tested these possibilities utilizing the puromycin aminonucleoside (PAN) model of renal injury in immortalized mouse podocytes. The cultured podocytes expressed PPAR-gamma mRNA at baseline but this was decreased by PAN. Pioglitazone, a pharmacologic agonist of PPAR-gamma, increased both PPAR-gamma mRNA and activity in injured podocytes, as assessed by a reporter plasmid assay. Further, pioglitazone significantly decreased PAN-induced podocyte apoptosis and necrosis while restoring podocyte differentiation. The PPAR-gamma agonist significantly restored expression of the cyclin-dependent kinase inhibitor p27 and the antiapoptotic molecule Bcl-xL while significantly decreasing proapoptotic caspase-3 activity. Pioglitazone tended to decrease PAN-induced transforming growth factor-beta (TGF-beta) mRNA expression. Our study shows that PPAR-gamma is normally expressed by podocytes and its activation is protective against PAN-induced apoptosis and necrosis. We postulate that this protective effect may be mediated in part by effects on p27 and TGF-beta expression.

MeSH Terms (18)

Animals Apoptosis bcl-X Protein Caspase Inhibitors Cell Proliferation Cells, Cultured Cyclin-Dependent Kinase Inhibitor p27 Kidney Glomerulus Mice Necrosis Pioglitazone Plasmids Podocytes PPAR gamma Puromycin Aminonucleoside RNA, Messenger Thiazolidinediones Transforming Growth Factor beta

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