PPAR? Activation Protects against Anti-Thy1 Nephritis by Suppressing Glomerular NF-?B Signaling.

ABSTRACT: The vast increase of chronic kidney disease (CKD) has attracted considerable attention worldwide, and the development of a novel therapeutic option against a representative kidney disease that leads to CKD, mesangial proliferative glomerulonephritis (MsPGN) would be significant. Peroxisome proliferator-activated receptor ? (PPAR?), a member of the steroid/nuclear receptor superfamily, is known to perform various physiological functions. Recently, we reported that PPAR? in activated mesangial cells exerted anti-inflammatory effects and that the deficiency of PPAR? resulted in high susceptibility to glomerulonephritis. To investigate whether PPAR? activation improves the disease activity of MsPGN, we examined the protective effects of a PPAR? agonist, clofibrate, in a well-established model of human MsPGN, anti-Thy1 nephritis, for the first time. This study demonstrated that pretreatment with clofibrate (via a 0.02% or 0.1% clofibrate-containing diet) continuously activated the glomerular PPAR?, which outweighed the PPAR? deterioration associated with the nephritic process. The PPAR? activation appeared to suppress the NF-?B signaling pathway in glomeruli by the induction of I?B?, resulting in the reduction of proteinuria and the amelioration of the active inflammatory pathologic glomerular changes. These findings suggest the antinephritic potential of PPAR?-related medicines against MsPGN. PPAR?-related medicines might be useful as a treatment option for CKD.

SUBMITTER: Hashimoto K 

PROVIDER: S-EPMC3363069 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature