Objective: To investigate the localization and expression of protein kinase C (PKC)-betaI, betaII in diabetic nephropathy (DN) mouse kidney and its relation to angiotensin receptor blocker telmisartan (Micardis).
Methods: Eighteen mice were divided into three groups: normal group, DN group and Micardis-treated group (n = 6, each group). The expression of PKC-betaI, betaII, transforming growth factor- beta 1 (TGF-beta1) and vascular endothelial growth factor (VEGF) in glomeruli was measured by semiquantitative immunofluorescence histochemistry, the localization of PKC-betaI, betaII was detected by confocal immunofluorescence laser scanning microscopy and the expression of PKC-betaI, betaII in renal cortex, outer and inner medulla were evaluated by semiquantitative Western blotting.
Results: Compared to normal mice, the expression of PKC-betaI and betaII on apical membrane of proximal tubule epithelial cells of DN mice was significantly increased, whereas the expression of PKC-betaII on cortical and inner medullary collecting duct was decreased. Western blotting detected increasing expression of PKC-betaI in the renal cortex and outer medulla (P < 0.01), and decreasing expression of PKC-betaII in renal cortex of DN mice (P < 0.01). Enhanced expression of PKC-betaI as well as TGF-beta1 and VEGF (P < 0.01) were shown in the glomeruli of DN mice, where the expression of PKC-betaII was decreased (P < 0.05). Meanwhile, PKC-betaI exhibited a positive correlation to TGF-beta1 (r = 0.649, P = 0.030), but no correlation to VEGF (r = 0.387, P = 0.079). Micardis could partly attenuate above changes.
Conclusion: The localization and expression of PKC-betaI, betaII are altered in DN mice, PKC-betaI, betaII may change the function of proximal tubule and PKC-betaI may contribute to glomerular hypertrophy through influencing the expression of glomerular TGF-beta1. Treatment with Micardis can partly improve the abnormal expression and distribution of PKC-betaI, betaII in kidneys of DN mice, which suggests that renin-angiotensin-system is implicated in the pathogenesis of DN by regulating the expression and activation of PKC-betaI, betaII isoforms.