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学科主题: 临床医学
题名:
Soluble epoxide hydrolase inhibition ameliorates proteinuria-induced epithelial-mesenchymal transition by regulating the PI3K-Akt-GSK-3 beta signaling pathway
作者: Liang, Yaoxian1; Jing, Ziyang1; Deng, Hui1; Li, Zhengqian2; Zhuang, Zhen1; Wang, Song1; Wang, Yue1
关键词: Soluble epoxide hydrolase ; Proteinuria ; Epithelial-mesenchymal transition ; Adriamycin-induced nephropathy
刊名: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
发表日期: 2015-07-17
DOI: 10.1016/j.bbrc.2015.05.020
卷: 463, 期:1-2, 页:70-75
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]: PROXIMAL TUBULAR CELLS ; EPOXYEICOSATRIENOIC ACIDS ; NEPHROPATHY ; FIBROSIS ; PI3K/AKT ; INFLAMMATION ; DISEASE ; KINASE ; KIDNEY ; DAMAGE
英文摘要:

Soluble epoxide hydrolase (sEH) plays an essential role in chronic kidney disease by hydrolyzing reno-protective epoxyeicosatrienoic acids to the corresponding inactive dihydroxyeicosatrienoic acids. However, there have been few mechanistic studies elucidating the role of sEH in epithelial-mesenchymal transition (EMT). The present study investigated, in vitro and in vivo, the role of sEH in proteinuria-induced renal tubular EMT and the underlying signaling pathway. We report that urinary protein (UP) induced EMT in cultured NRK-52E cells, as evidenced by decreased E-cadherin expression, increased alpha-smooth muscle actin (alpha-SMA) expression, and the morphological conversion to a myofibroblast-like phenotype. UP incubation also resulted in upregulated sEH, activated phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB/Akt) signaling and increased phosphorylated glycogen synthase kinase-3 beta (GSK-3 beta). The PI3K inhibitor LY-294002 inhibited phosphorylation of Akt and GSK-3 beta as well as blocking EMT. Importantly, pharmacological inhibition of sEH with 12-(3-adamantan-1-yl- ureido)dodecanoic acid (AUDA) markedly suppressed PI3K-Akt activation and GSK-3 beta phosphorylation. EMT associated E-cadherin suppression, alpha-SMA elevation and phenotypic transition were also attenuated by AUDA. Furthermore, in rats with chronic proteinuric renal disease, AUDA treatment inhibited PI3K-Akt activation and GSK-3 beta phosphorylation, while attenuating levels of EMT markers. Overall, our findings suggest that sEH inhibition ameliorates proteinuria-induced renal tubular EMT by regulating the PI3K-Akt-GSK-3 beta signaling pathway. Targeting sEH might be a potential strategy for the treatment of EMT and renal fibrosis. (C) 2015 Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: 81070213
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000356753400013
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57772
Appears in Collections:北京大学第三临床医学院_肾内科_期刊论文

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作者单位: 1.Peking Univ, Dept Nephrol, Hosp 3, Beijing 100191, Peoples R China
2.Peking Univ, Dept Anesthesiol, Hosp 3, Beijing 100191, Peoples R China

Recommended Citation:
Liang, Yaoxian,Jing, Ziyang,Deng, Hui,et al. Soluble epoxide hydrolase inhibition ameliorates proteinuria-induced epithelial-mesenchymal transition by regulating the PI3K-Akt-GSK-3 beta signaling pathway[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2015,463(1-2):70-75.
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