The PPARγ agonist pioglitazone ameliorates aging-related progressive renal injury

Hai Chun Yang, Sebastien Deleuze, Yiqin Zuo, Sebastian A. Potthoff, Li Jun Ma, Agnes B. Fogo

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against nondiabetic chronic kidney disease in experimental models. Here, we found that the PPAR-γ agonist pioglitazone protected against renal injury in aging; it reduced proteinuria, improved GFR, decreased sclerosis, and alleviated cell senescence. Increased local expression of PPAR-γ paralleled these changes. Underlying mechanisms included increased expression of klotho, decreased systemic and renal oxidative stress, and decreased mitochondrial injury. Pioglitazone also regulated p66 Shc phosphorylation, which integrates many signaling pathways that affect mitochondrial function and longevity, by reducing protein kinase C-β. These results suggest that PPAR-γ agonists may benefit aging-related renal injury by improving mitochondrial function.

Original languageEnglish (US)
Pages (from-to)2380-2388
Number of pages9
JournalJournal of the American Society of Nephrology
Volume20
Issue number11
DOIs
StatePublished - Nov 2009
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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