[Protein kinase C-betaI, betaII in mouse diabetic nephropathy kidney and its relation to nephroprotective actions of the angiotensin receptor blocker telmisartan].
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.


CONCLUSIONS
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.
Yao
Li-jun
LJ
Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Wang
Jian-qing
JQ
Deng
An-guo
AG
Liu
Jian-she
JS
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D005455:Fluorescent Antibody Technique; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000378:metabolism*; D000077333:Telmisartan; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D007527:Isoenzymes; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D011493:Protein Kinase C; D000077333:Telmisartan