title: Peroxisome proliferator-activated receptor δ downregulates the expression of the receptor for advanced glycation end products and pro-inflammatory cytokines in the kidney of streptozotocin-induced diabetic mice.
abstract: Activation of peroxisome proliferator-activated receptor δ (PPARδ) plays board beneficial effects in treating metabolic syndrome. The aim of this study is to examine whether PPARδ 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 PPARδ agonist, L-165041 (5 μM/kg, intraperitoneal) once daily for 10 days and high glucose-treated cultured HEK cells were also used. After L-165041 treatment, serum TNFα, 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-κB, RAGE and IL-6 expressions in HEK293 cells. These effects were inhibited by L-165041 and specific RAGE siRNA transfection. This study demonstrated that PPARδ may play a beneficial role in preventing diabetic nephropathy. Its downstream signaling may include RAGE and NF-κB pathway. Target on PPARδ will provide new meaningful therapies to patients with diabetic nephropathy.
authors: Department and Institute of Life Science, Fu-Jen Catholic University, Taipei, Taiwan, ROC. 071558@mail.fju.edu.tw
authors: Yao-Jen
authors: YJ
authors: Liang
authors: Siang-An
authors: SA
authors: Chen
authors: Jhih-Hao
authors: JH
authors: Jian
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000517:prevention & control; D015536:Down-Regulation; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D047494:PPAR delta / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D010642:Phenoxyacetates / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C520164:4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid; D016207:Cytokines; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D047494:PPAR delta; D010642:Phenoxyacetates