Submitted on October 16, 2008
Revised on December 11, 2008
Accepted on January 1, 2009
Glomerular 20-HETE, EETs, and TGF-
in Diabetic Nephropathy
Pengcheng Luo1, Yiqiang Zhou1, Hsin-Hsin Chang1, Jie Zhang2, Tsugio Seki1, Cong-Yi Wang, Edward W. Inscho1, and Mong-Heng Wang1*
1 Medical College of Georgia
2 Renmin Hospital of Wuhan University, Hubei Province, P.R. China
* To whom correspondence should be addressed. E-mail: mwang{at}mail.mcg.edu.
The early stage of diabetic nephropathy (DN) is linked to proteinuria. TGF-
1 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- 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 weeks 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 as 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-1 levels were significant 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 TGF1 and urinary protein excretion. These results demonstrate that hyperglycemia increases TGF- 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.
