Open AccessGlomerular 20-HETE, EETs, and TGF-β1 in diabetic nephropathy
Author(s) -
Pengfei Luo,
Yiqiang Zhou,
Hsin Hsin Chang,
Jie Zhang,
Tsugio Seki,
Cong Yi Wang,
Edward W. Inscho,
Mong Heng Wang
Publication year - 2009
Publication title -
american journal of physiology. renal physiology./american journal of physiology. renal physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.335
H-Index - 169
eISSN - 1931-857X
pISSN - 1522-1466
DOI - 10.1152/ajprenal.90613.2008
Subject(s) - medicine , endocrinology , streptozotocin , diabetic nephropathy , hyperlipidemia , diabetes mellitus , kidney , nephropathy , excretion , triglyceride , chemistry , cholesterol
The early stage of diabetic nephropathy (DN) is linked to proteinuria. Transforming growth factor (TGF)-beta1 increases glomerular permeability to albumin (P(alb)), whereas 20-HETE and EETs reduce P(alb). To investigate the impact of hyperglycemia and hyperlipidemia on 20-HETE, EETs, and TGF-beta1 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-beta1 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-beta1 and urinary protein excretion. These results demonstrate that hyperglycemia increases TGF-beta1 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.