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学科主题临床医学
Soluble epoxide hydrolase inhibition ameliorates proteinuria-induced epithelial-mesenchymal transition by regulating the PI3K-Akt-GSK-3 beta signaling pathway
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
2015-07-17
DOI10.1016/j.bbrc.2015.05.020
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
WOS记录号WOS:000356753400013
项目编号81070213
资助机构National Natural Science Foundation of China
引用统计
被引频次:10[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57772
专题北京大学第三临床医学院_肾内科
北京大学第二临床医学院_肾内科
北京大学第三临床医学院_麻醉科
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
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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.
APA Liang, Yaoxian.,Jing, Ziyang.,Deng, Hui.,Li, Zhengqian.,Zhuang, Zhen.,...&Wang, Yue.(2015).Soluble epoxide hydrolase inhibition ameliorates proteinuria-induced epithelial-mesenchymal transition by regulating the PI3K-Akt-GSK-3 beta signaling pathway.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,463(1-2),70-75.
MLA Liang, Yaoxian,et al."Soluble epoxide hydrolase inhibition ameliorates proteinuria-induced epithelial-mesenchymal transition by regulating the PI3K-Akt-GSK-3 beta signaling pathway".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 463.1-2(2015):70-75.
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