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Methionine sulfoxide reductase A deficiency exacerbates progression of kidney fibrosis induced by unilateral ureteral obstruction

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Author(s)
Jee InKimMiRaNohKiYoungKimHee-SeongJangHwa-YoungKimKwon MooPark
Keimyung Author(s)
Kim, Jee In
Department
Dept. of Molecular Medicine (분자의학)
Journal Title
Free Radical Biology and Medicine
Issued Date
2015
Volume
89
Keyword
Methionine sulfoxidereductaseMsrAUreteralobstructionFibrosisOxidativestressInflammation
Abstract
Methionine sulfoxide reductase A (MsrA), which stereospecifically catalyzes the reduction of methionine-S-sulfoxide, is an important reactive oxygen species (ROS) scavenger. Tissue fibrosis is a maladaptive repair process following injury, associated with oxidative stress. In this study, we investigated the role of MsrA in unilateral ureteral obstruction (UUO)-induced kidney fibrosis and its underlying mechanisms by using MsrA gene-deleted mice (MsrA−/−). MsrA deletion increased collagen deposition in the interstitium and the expression of collagen III and α-smooth muscle actin in the UUO kidneys, indicating that MsrA deficiency exacerbated the progression of UUO-induced kidney fibrosis. UUO reduced the kidney expression of MsrA, MsrB1, and MsrB2, thereby decreasing MsrA and MsrB activity. UUO increased hydrogen peroxide and lipid peroxidation levels and the ratio of oxidized glutathione (GSSG) to total glutathione (GSH) in the kidneys. The UUO-induced elevations in the levels of these oxidative stress markers and leukocyte markers were much higher in the MsrA−/− than in the MsrA+/+ kidneys, the latter suggesting that the exacerbated kidney fibrosis in MsrA−/− mice was associated with enhanced inflammatory responses. Collectively, our data suggest that MsrA plays a protective role in the progression of UUO-induced kidney fibrosis via suppression of fibrotic responses caused by oxidative stress and inflammation.
Keimyung Author(s)(Kor)
김지인
Publisher
School of Medicine
Citation
Jee InKim et al. (2015). Methionine sulfoxide reductase A deficiency exacerbates progression of kidney fibrosis induced by unilateral ureteral obstruction. Free Radical Biology and Medicine, 89, 201–208. doi: 10.1016/j.freeradbiomed.2015.07.018
Type
Article
ISSN
0891-5849
Source
http://lps3.linkinghub.elsevier.com.proxy.dsmc.or.kr/retrieve/pii/S0891-5849(15)00342-1
DOI
10.1016/j.freeradbiomed.2015.07.018
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/32999
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
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