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.
Conclusion: 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.