title: L-165,041, troglitazone and their combination treatment to attenuate high glucose-induced receptor for advanced glycation end products (RAGE) expression.
abstract: Diabetic nephropathy is the leading cause of end-stage renal disease in the most developed countries of the world. Hyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) production, pro-inflammatory cytokine secretion, and oxidative stress activation play major roles in kidney cell injury and apoptosis. Peroxisome proliferator-activated receptor-gamma (PPARγ) agonists are used clinically as insulin sensitizers. This study evaluated the renoprotective effect of PPARγ (troglitazone) and PPARδ (L-165,041) agonists on human embryonic kidney 293 (HEK) and mesangial cells. Troglitazone (10 μM) and L-165,041 (1 μM) significantly inhibited high glucose (25mM)-induced interleukin-6 and TNF-α production, RAGE expression and NF-κB translocation in HEK cells. Furthermore, Troglitazone (10 μM) and L-165,041(1 μM) significantly increased SOD expression and attenuated apoptosis in HEK and mesangial cells. The inhibitory effect between 1 μM L-165,041 and 10 μM troglitazone showed no difference. Furthermore L-165,041 and troglitazone together did not increase the effects. These results provide important information for future application of PPAR agonists in diabetic nephropathy treatment.
authors.affiliation: Department and Institute of Life Science, Fu-Jen Catholic University, Taipei, Taiwan.
authors.forename: Yao-Jen
authors.initials: YJ
authors.lastname: Liang
authors.forename: Jhin-Hao
authors.initials: JH
authors.lastname: Jian
authors.forename: Chao-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Hsu
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Shih
authors.forename: Jyh-Gang
authors.initials: JG
authors.lastname: Leu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D047494:PPAR delta / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists; D010642:Phenoxyacetates / Q000494:pharmacology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
chemical_list: C520164:4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid; D002839:Chromans; D016207:Cytokines; D016328:NF-kappa B; D047494:PPAR delta; D047495:PPAR gamma; D010642:Phenoxyacetates; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D045162:Thiazolidinediones; D000077288:Troglitazone; D005947:Glucose
keywords: Apoptosis; Diabetic nephropathy; PPAR delta; PPAR gamma; RAGE