The PPARgamma agonist pioglitazone ameliorates aging-related progressive renal injury.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) 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-gamma agonist pioglitazone protected against renal injury in aging; it reduced proteinuria, improved GFR, decreased sclerosis, and alleviated cell senescence. Increased local expression of PPAR-gamma 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-beta. These results suggest that PPAR-gamma agonists may benefit aging-related renal injury by improving mitochondrial function.
Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Hai-Chun
HC
Yang
Sebastien
S
Deleuze
Yiqin
Y
Zuo
Sebastian A
SA
Potthoff
Li-Jun
LJ
Ma
Agnes B
AB
Fogo
D000367:Age Factors; D000375:Aging; D000818:Animals; D018450:Disease Progression; D007674:Kidney Diseases / Q000517:prevention & control*; D008297:Male; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000627:therapeutic use*
D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone