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学科主题临床医学
Upregulation of soluble epoxide hydrolase in proximal tubular cells mediated proteinuria-induced renal damage
Wang, Qian1,3; Pang, Wei2; Cui, Zhuan1; Shi, Junbao1; Liu, Yan2; Liu, Bo2; Zhou, Yunfeng2; Guan, Youfei2; Hammock, Bruce D.4,5; Wang, Yue1; Zhu, Yi2
关键词Glomerulonephritis Soluble Epoxide Hydrolase Proteinuria Inflammation Epithelial-mesenchymal Transition
刊名AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
2013
DOI10.1152/ajprenal.00129.2012
304期:2页:F168-F176
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Physiology ; Urology & Nephrology
研究领域[WOS]Physiology ; Urology & Nephrology
关键词[WOS]ENDOTHELIUM IN-VITRO ; EPOXYEICOSATRIENOIC ACIDS ; BLOOD-PRESSURE ; HUMAN TISSUES ; HYPERTENSION ; INFLAMMATION ; INHIBITION ; KIDNEY ; PATHOPHYSIOLOGY ; LOCALIZATION
英文摘要

Wang Q, Pang W, Cui Z, Shi J, Liu Y, Liu B, Zhou Y, Guan Y, Hammock BD, Wang Y, Zhu Y. Upregulation of soluble epoxide hydrolase in proximal tubular cells mediated proteinuria-induced renal damage. Am J Physiol Renal Physiol 304: F168-F176, 2013. First published November 14, 2012; doi:10.1152/ajprenal.00129.2012.-Epoxyeicosatrienoic acids, hydrolyzed by soluble epoxide hydrolase (sEH), have multiple biological functions, including the regulation of vascular tone, renal tubular transport, and being anti-inflammatory. Inhibitors of sEH have been demonstrated to be antihypertensive and renal protective. To elucidate the role of sEH in glomerulonephritis, we first determined the expression of sEH in human kidney by examining biopsies from 153 patients with a variety of glomerulonephritis, including minimal-change, membranous, and IgA nephropathy. Immunohistochemical staining of frozen kidney biopsy samples revealed sEH preferentially expressed in the renal proximal tubular cells, and its expression increased in all patients with glomerulonephritis. The level of sEH in the cortex was positively correlated with proteinuria and negatively with serum albumin level. To investigate the role of sEH in proteinuria-induced renal damage, we incubated purified urine protein from patients with rat renal proximal tubular epithelial cells in vitro. The level of sEH was elevated, as were monocyte chemoattractant protein 1 and the process of tubular epithelial-to-mesenchymal transition, characterized with increased alpha-smooth muscle actin (alpha-SMA) and decreased Ecadherin. These effects were attenuated by administration of a potent sEH inhibitor and mimicked with adenovirus-mediated sEH overexpression. In adriamycin-induced nephropathic mice, sEH inhibitor did not ameliorate proteinuria or level of serum albumin but reduced the long-term elevated serum creatinine level, interstitial inflammation, fibrosis, and alpha-SMA expression. Thus upregulation of sEH in proximal tubular cells in chronic proteinuric kidney diseases may mediate proteinuria-induced renal damage; sEH inhibition by increasing renal eicosanoid levels could prevent the progression of chronic proteinuric kidney diseases.

语种英语
WOS记录号WOS:000313739600004
项目编号2010CB912504 ; 2012CB517504 ; 30971063 ; 81130002 ; 81070213 ; RO1 HL059699 ; RO1 ES02710
资助机构Major National Basic Research Grant of China ; National Natural Science Foundation of China ; "111" plan of China ; National Institute of Environmental Health Sciences, NIH
引用统计
被引频次:11[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/400002259/55683
专题北京大学基础医学院
北京大学第三临床医学院_肾内科
作者单位1.Peking Univ, Hosp 3, Dept Nephrol, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Key Lab Mol Cardiovasc Sci,Minist Educ, Beijing 100191, Peoples R China
3.Zhengzhou Univ, Affiliated Hosp 1, Dept Geriatr Med, Zhengzhou, Henan Province, Peoples R China
4.Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA
5.Univ Calif Davis, Ctr Canc, Davis, CA 95616 USA
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GB/T 7714
Wang, Qian,Pang, Wei,Cui, Zhuan,et al. Upregulation of soluble epoxide hydrolase in proximal tubular cells mediated proteinuria-induced renal damage[J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY,2013,304(2):F168-F176.
APA Wang, Qian.,Pang, Wei.,Cui, Zhuan.,Shi, Junbao.,Liu, Yan.,...&Zhu, Yi.(2013).Upregulation of soluble epoxide hydrolase in proximal tubular cells mediated proteinuria-induced renal damage.AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY,304(2),F168-F176.
MLA Wang, Qian,et al."Upregulation of soluble epoxide hydrolase in proximal tubular cells mediated proteinuria-induced renal damage".AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 304.2(2013):F168-F176.
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