Korean J Nephrol.  2007 Sep;26(5):516-525.

Effects of Angiotensin II on ZO-1 in Glomerular Epithelial Cells

• Koo HH
• Ha TS

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.

Keyword

Angiotensin II; Angiotensin II type 1 receptor blockers; Podocyte; Zonula adherens

MeSH Terms

Actin Cytoskeleton
Adherens Junctions
Angiotensin II Type 1 Receptor Blockers
Angiotensin II*
Angiotensin Receptor Antagonists
Angiotensins*
Blotting, Western
Cytoplasm
Diaphragm
Epithelial Cells*
Losartan
Microscopy, Confocal
Podocytes
Receptor, Angiotensin, Type 1
RNA, Messenger
Angiotensin II
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Angiotensins
Losartan
RNA, Messenger
Receptor, Angiotensin, Type 1