Effect of losartan on the glomerular protein expression profile of type 2 diabetic KKAy mice

To investigate the pathogenesis of diabetic nephropathy (DN) and to search for novel therapeutic targets, the glomerular protein expression profile of KKAy mice treated by losartan was analyzed by two-dimensional differential gel electrophoresis (2D-DIGE).

The eight-week-old KKAy mice were divided into the losartan treatment group and the non-treatment group, and C57BL/6 mice were used as the control group. After 12 weeks treatment, glomeruli were isolated by abdominal perfusion with magnetic beads, and the glomerular proteins were extracted. The glomerular protein expression profiles were investigated using 2D-DIGE and MALDI-TOF mass spectrometry. Western blot analysis was used to confirm the results of proteomics.

Losartan treatment improved albuminuria and renal pathologic lesion of KKAy mice. A total of 62 glomerular proteins were differentially expressed between the KKAy losartan treatment mice and KKAy non-treatment mice. Among them, the expression of 28 proteins were up-regulated, including glycerokinase, sulfite oxidase, glycine amidinotransferase, and adenosylhomocysteinase. The expression of 13 proteins were down-regulated, including 3-mercaptopyruvate sulfurtransferase, ATP synthase subunit d, 60 kDa heat shock protein, and 75 kDa glucose-regulated protein(GRP75). A total of six proteins were found to be differentially expressed between the KKAy non-treatment mice and C57BL/6 mice glomeruli, and their differential expression was suppressed by losartan treatment, including mitochondrial ATP synthase subunit d, GRP75, and selenium-binding protein 1 et al.

Treatment with losartan suppresses the differential expression of mitochondrial ATP synthase subunit d, GRP75, selenium-binding protein 1 etc. In diabetic KKAy mice glomeruli, may play a renoprotective role by reducing glomerular mitochondrial ROS genesis and inhibiting oxidative stress.