Peroxisome proliferator-activated receptor delta downregulates the expression of the receptor for advanced glycation end products and pro-inflammatory cytokines in the kidney of streptozotocin-induced diabetic mice.

摘要

Activation of peroxisome proliferator-activated receptor delta (PPARdelta) plays board beneficial effects in treating metabolic syndrome. The aim of this study is to examine whether PPARdelta alters the expression of the receptor for advanced glycation end products (RAGE) and downstream pro-inflammatory cytokines in diabetic nephropathy. Streptozotocin-induced diabetic mice (STZ mice) were injected with a PPARdelta agonist, L-165041 (5 muM/kg, intraperitoneal) once daily for 10 days and high glucose-treated cultured HEK cells were also used. After L-165041 treatment, serum TNFalpha, IL-6 and IL-1 levels were significantly decreased in STZ mice. RAGE mRNA and protein expression were both decreased by L-165041 in kidney tissues of STZ mice. The high glucose incubation increased NF-kappaB, RAGE and IL-6 expressions in HEK293 cells. These effects were inhibited by L-165041 and specific RAGE siRNA transfection. This study demonstrated that PPARdelta may play a beneficial role in preventing diabetic nephropathy. Its downstream signaling may include RAGE and NF-kappaB pathway. Target on PPARdelta will provide new meaningful therapies to patients with diabetic nephropathy.