Korean Journal of Nephrology 2007;26(5):516-525.
Effects of Angiotensin II on ZO-1 in Glomerular Epithelial Cells
Hyun-Hoe Koo, M.D. and Tae-Sun Ha, M.D.
Department of Pediatrics, College of Medicine, Chungbuk National University Cheongju, Korea
안지오텐신 II의 사구체 상피세포 ZO-1에 대한 영향
구현회, 하태선
충북대학교 의과대학 소아과학교실
Abstract
Purpose : Angiotensin II plays a potent role in renal injury not only by vasoconstrictive effects but also by biochemical effects. We investigated the effect of angiotensin II on ZO-1 (zonular occludens-1), a component of the slit diaphragm domain connecting slit diaphragm structure and actin cytoskeleton, in the glomerular epithelial cells (podocytes) for the glomerular damage. We tried to find that this effect could be prevented by losartan, an angiotensin II type 1 receptor blocker. Methods : Glomerular epithelial cells were treated with various concentrations of angiotensin II and losartan. The distribution of ZO-1 was observed by confocal microscope and the change of ZO-1 expression was measured by Western blotting and RT-PCR. Results : The intensities of fluorescences and bands of ZO-1 protein were decreased by angiotensin II in a dose-dependent manner by confocal microscopy and Western blot analysis, respectively. ZO-1 also moved from peripheral to inner cytoplasm and lost its linear pattern. These distributional changes of ZO-1 protein by angiotensin II were reversed by losartan in a dose-dependent manner. Angiotensin II reduced the amount and mRNA expresssion of ZO-1 which were also reversed by losartan. Conclusion : Angiotensin II decreases the amount of ZO-1 protein and changes its localization through angiotensin II type 1 receptor. These findings suggest that angiotensin II-added condition induces the cytoplasmic translocation and suppresses the production of ZO-1 in podocytes at transcriptional level, and could be prevented by angiotensin receptor antagonists.
Key Words: Angiotensin II, Angiotensin II type 1 receptor blockers, Podocyte, Zonula adherens


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