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Clusterin/Apolipoprotein J Attenuates Angiotensin II-Induced Renal Fibrosis

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Author(s)
Gwon-Soo JungJae-Han JeonYun-A JungYeon-Kyung ChoiHye-Soon KimJung-Guk KimKeun-Gyu ParkMi-Kyung KimIn-Kyu Lee
Keimyung Author(s)
Kim, Hye SoonKim, Mi Kyung
Department
Dept. of Internal Medicine (내과학)
Journal Title
PLoS One
Issued Date
2014
Volume
9
Issue
8
Abstract
The blockade of angiotensin II (Ang II) is a major therapeutic strategy for diabetic nephropathy. The main roles of Ang II in renal disease are mediated via the Ang type 1 receptor (AT1R). Upregulation of clusterin/apolipoprotein J has been reported in nephropathy models, suggesting it has a protective role in nephropathogenesis. Here, we studied how clusterin acts against Ang II-induced renal fibrosis. Levels of AT1R and fibrotic markers in clusterin-/- mice and Ang II infused rats transfected with an adenovirus encoding clusterin were evaluated by immunoblot analysis, real time RT-PCR, and immunohistochemical staining. The effect of clusterin on renal fibrosis was evaluated in NRK-52E cells, a cultured renal tubular epithelial cell line, using immunoblot analysis and real time RT-PCR. Nuclear localization of NF-κB was evaluated using immunofluorecence and co-immunoprecipitation. Renal fibrosis and expression of AT1R was higher in the kidneys of clusterin-/- mice than in those of wild-type mice. Furthermore, loss of clusterin accelerated Ang II-stimulated renal fibrosis and AT1R expression. Overexpression of clusterin in proximal tubular epithelial cells decreased the levels of Ang II-stimulated fibrotic markers and AT1R. Moreover, intrarenal delivery of clusterin attenuated Ang II-mediated expression of fibrotic markers and AT1R in rats. Fluorescence microscopy and co-immunoprecipitation in conjunction with western blot revealed that clusterin inhibited Ang II-stimulated nuclear localization of p-NF-κB via a direct physical interaction and subsequently decreased the AT1R level in proximal tubular epithelial cells. These data suggest that clusterin attenuates Ang II-induced renal fibrosis by inhibition of NF-κB activation and subsequent downregulation of AT1R. This study raises the possibility that clusterin could be used as a therapeutic target for Ang II-induced renal diseases.
Keimyung Author(s)(Kor)
김혜순
김미경
Publisher
School of Medicine
Citation
Gwon-Soo Jung et al. (2014). Clusterin/Apolipoprotein J Attenuates Angiotensin II-Induced Renal Fibrosis. PLoS One, 9(8), e105635–e105635. doi: 10.1371/journal.pone.0105635
Type
Article
ISSN
1932-6203
DOI
10.1371/journal.pone.0105635
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33685
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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