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Am J Physiol Renal Physiol 296: F556-F563, 2009. First published January 7, 2009; doi:10.1152/ajprenal.90613.2008
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Glomerular 20-HETE, EETs, and TGF-β1 in diabetic nephropathy

Pengcheng Luo,1,2 Yiqiang Zhou,1 Hsin-Hsin Chang,1 Jie Zhang,2 Tsugio Seki,1 Cong-Yi Wang,3 Edward W. Inscho,1 and Mong-Heng Wang1

1Department of Physiology, Medical College of Georgia, Augusta; 3Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, Georgia; and 2Department of Urology, Renmin Hospital of Wuhan University, Hubei Province, People's Republic of China

Submitted 16 October 2008 ; accepted in final form 1 January 2009

The early stage of diabetic nephropathy (DN) is linked to proteinuria. Transforming growth factor (TGF)-β1 increases glomerular permeability to albumin (Palb), whereas 20-HETE and EETs reduce Palb. To investigate the impact of hyperglycemia and hyperlipidemia on 20-HETE, EETs, and TGF-β1 in the glomeruli, rats were divided into four groups: ND rats were fed a normal diet, HF rats were fed a high-fat diet, STZ rats were treated with 35 mg/kg of streptozotocin, and HF/STZ rats were fed a HF diet and treated with STZ. After 10 wk on these regimens, blood glucose, urinary albumin, serum cholesterol, serum triglyceride levels, and the kidney-to-body weight ratio were significantly elevated in STZ and HF/STZ rats compared with HF and ND rats. STZ and HF/STZ rats had histopathologic changes and abnormal renal hemodynamics. Expression of glomerular CYP4A, enzymes for 20-HETE production, was significantly decreased in STZ rats, whereas expression of glomerular CYP2C and CYP2J, enzymes for EETs production, was significantly decreased in both STZ and HF/STZ rats. Moreover, glomerular TGF-β1 levels were significantly greater in STZ and HF/STZ rats than in HF and ND rats. Five-week treatment of STZ rats with clofibrate induced glomerular CYP4A expression and 20-HETE production, but reduced glomerular TGF-β1 and urinary protein excretion. These results demonstrate that hyperglycemia increases TGF-β1 but decreases 20-HETE and EETs production in the glomeruli, changes that may be important in causing glomerular damage in the early stage of DN.

CYP-derived eicosanoids; streptozotocin; kidney


Address for reprint requests and other correspondence: M.-H. Wang, Dept. of Physiology, Medical College of Georgia, Augusta, GA 30912 (e-mail: mwang{at}mail.mcg.edu)






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