Effect of losartan on cyclooxygenase-2 expression in normal human mesangial cells and kidneys of rats with diabetic nephropathy.
OBJECTIVE
To investigate the effect of high glucose and losartan on cell proliferation and cyclooxygenase-2 (COX2) expression in normal human mesangial cells (NHMCs), and to examine the effect of losartan on COX2 and transforming growth factor-beta1 (TGF-beta1) expression in a model of diabetic nephropathy (DN).


METHODS
NHMCs were cultured in vitro in high glucose media with or without losartan. NHMCs proliferation and COX2 expression were determined by WST-1, Western blot, and RT-PCR. The rat model of DN was produced by injections of streptozocin (STZ). After the treatment with losartan for 4 weeks, glomerular hypertrophy, urinary thromboxane B2 (TXB2) and 24 h urinary protein counts were measured, and COX2 and TGF-beta1 expressions were investigated using immunohistochemical techniques and RT-PCR.


RESULTS
Losartan dose-dependently inhibited the proliferation of NHMCs in response to high glucose. Losartan also decreased COX2 expression in NHMCs at high or low glucose concentrations. In vivo experiments found kidney weight/body weight (KW/BW), urinary TXB2 and 24 h urinary protein counts increased significantly in the DN group. Losartan reduced KW/BW, urinary TXB2, and 24 h urinary protein counts and significantly suppressed the over-expression of COX2 and TGF-beta1.


CONCLUSIONS
Losartan reduces COX2 expression in NHMCs,especially at high glucose concentrations. Losartan could suppress the expression of COX2 and TGF-beta1 in the kidney of DN rats and attenuate the renal lesions caused by DN.
Zhou
Qiao-Ling
QL
Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, China. zhouqling@yahoo.com.cn
Peng
Wei-Sheng
WS
Yuichiro
Yasumoto
Y
Liu
Zhi-Chun
ZC
Yang
Jing-Hua
JH
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000201:enzymology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D051546:Cyclooxygenase 2; D019808:Losartan