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The protective effect of klotho against contrast-associated acute kidney injury via the antioxidative effect

Authors
 Hyung Jung Oh  ;  Hyewon Oh  ;  Bo Young Nam  ;  Je Sung You  ;  Dong-Ryeol Ryu  ;  Shin-Wook Kang  ;  Yong Eun Chung 
Citation
 AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, Vol.317(4) : F881-F889, 2019 
Journal Title
 AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 
ISSN
 1931-857X 
Issue Date
2019
Keywords
acute kidney injury ; apoptosis ; oxidative stress
Abstract
As oxidative stress is one major factor behind contrast-associated acute kidney injury (CA-AKI), we investigated the protective effect of klotho against CA-AKI via the antioxidative effect. In in vitro experiments, cells (NRK-52E) were divided into the following three groups: control, iopamidol, or iopamidol + recombinant klotho (rKL) groups. Moreover, cell viability was measured with the Cell Counting Kit-8 assay, and oxidative stress was examined with 2',7'-dichlorodihydrofluorescein diacetate fluorescence intensity. RT-PCR and Western blot analysis were performed to assess propidium iodide klotho expression, and Bax-to-Bcl-2 and apoptosis ratios were evaluated with annexin V/Hoechst 33342 staining. Furthermore, we knocked down the klotho gene using siRNA to verify the endogenous effect of klotho. In our in vivo experiments, oxidative stress was evaluated with the thiobarbituric acid-reactive substance assay, and apoptosis was evaluated with the Bax-to-Bcl-2 ratio and cleaved caspase-3 immunohistochemistry. Additionally, cell and tissue morphology were investigated with transmission electron microscopy. In both in vitro and in vivo experiments, mRNA and protein expression of klotho significantly decreased in CA-AKI mice compared with control mice, whereas oxidative stress and apoptosis markers were significantly increased in CA-AKI mice. However, rKL supplementation mitigated the elevated apoptotic markers and oxidative stress in the CA-AKI mouse model and improved cell viability. In contrast, oxidative stress and apoptotic markers were more aggravated when the klotho gene was knocked down. Moreover, we found more cytoplasmic vacuoles in the CA-AKI mouse model using transmission electron microscopy but fewer cytoplasmic vacuoles in rKL-supplemented cells. The present study shows that klotho in proximal tubular cells can protect against CA-AKI via an antioxidative effect.
Full Text
https://www.physiology.org/doi/full/10.1152/ajprenal.00297.2018
DOI
10.1152/ajprenal.00297.2018
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
You, Je Sung(유제성) ORCID logo https://orcid.org/0000-0002-2074-6745
Chung, Yong Eun(정용은) ORCID logo https://orcid.org/0000-0003-0811-9578
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/173048
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