期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 715, 期 1-3, 页码 33-38出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2013.06.026
关键词
PPAR gamma; PPAR delta; Diabetic nephropathy; RAGE; Apoptosis
资金
- Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan [SKH-8302-100-DR-03]
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 (PPAR gamma) agonisis are used clinically as insulin sensitizers. This study evaluated the renoprotective effect of PPAR gamma (troglitazone) and PPAR delta (L165,041) agonists on human embryonic kidney 293 (HEK) and mesangial cells. Troglitazone (10 mu M) and L165,041 (1 mu M) significantly inhibited high glucose (25 mM)-induced interleukin-6 and TNF-alpha production, RAGE expression and NF-kappa B translocation in HEK cells. Furthermore, Troglitazone (10 mu M) and L-165,041(1 mu M) significantly increased SOD expression and attenuated apoptosis in HEK and mesangial cells. The inhibitory effect between 1 mu M L-165,041 and 10 mu M 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. (C) 2013 Elsevier B.V. All rights reserved.
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