Genetic Deletion of Soluble Epoxide Hydrolase Attenuates Inflammation and Fibrosis in Experimental Obstructive Nephropathy

Soluble epoxide hydrolase (sEH) is abundantly expressed in kidney and plays a potent role in regulating inflammatory response in inflammatory diseases. However, the role of sEH in progression of chronic kidney diseases such as obstructive nephropathy is still elusive. In current study, wild-type (WT...

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Main Authors: Chin-Wei Chiang, Hsueh-Te Lee, Der-Cherng Tarng, Ko-Lin Kuo, Li-Ching Cheng, Tzong-Shyuan Lee
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2015/693260
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author Chin-Wei Chiang
Hsueh-Te Lee
Der-Cherng Tarng
Ko-Lin Kuo
Li-Ching Cheng
Tzong-Shyuan Lee
author_facet Chin-Wei Chiang
Hsueh-Te Lee
Der-Cherng Tarng
Ko-Lin Kuo
Li-Ching Cheng
Tzong-Shyuan Lee
author_sort Chin-Wei Chiang
collection DOAJ
description Soluble epoxide hydrolase (sEH) is abundantly expressed in kidney and plays a potent role in regulating inflammatory response in inflammatory diseases. However, the role of sEH in progression of chronic kidney diseases such as obstructive nephropathy is still elusive. In current study, wild-type (WT) and sEH deficient (sEH−/−) mice were subjected to the unilateral ureteral obstruction (UUO) surgery and the kidney injury was evaluated by histological examination, western blotting, and ELISA. The protein level of sEH in kidney was increased in UUO-treated mice group compared to nonobstructed group. Additionally, UUO-induced hydronephrosis, renal tubular injury, inflammation, and fibrosis were ameliorated in sEH−/− mice with the exception of glomerulosclerosis. Moreover, sEH−/− mice with UUO showed lower levels of inflammation-related and fibrosis-related protein such as monocyte chemoattractant protein-1, macrophage inflammatory protein-2, interleukin-1β (IL-1β), IL-6, inducible nitric oxide synthase, collagen 1A1, and α-actin. The levels of superoxide anion radical and hydrogen peroxide as well as NADPH oxidase activity were also decreased in UUO kidneys of sEH−/− mice compared to that observed in WT mice. Collectively, our findings suggest that sEH plays an important role in the pathogenesis of experimental obstructive nephropathy and may be a therapeutic target for the treatment of obstructive nephropathy-related diseases.
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spelling doaj-art-e65d8a30941e4895b03d07ee5ba835262025-02-03T01:28:49ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/693260693260Genetic Deletion of Soluble Epoxide Hydrolase Attenuates Inflammation and Fibrosis in Experimental Obstructive NephropathyChin-Wei Chiang0Hsueh-Te Lee1Der-Cherng Tarng2Ko-Lin Kuo3Li-Ching Cheng4Tzong-Shyuan Lee5Department of Physiology, National Yang-Ming University, Taipei 11221, TaiwanInstitute of Anatomy and Cell Biology, National Yang-Ming University, Taipei 11221, TaiwanDepartment of Physiology, National Yang-Ming University, Taipei 11221, TaiwanDivision of Nephrology, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei 23142, TaiwanDepartment of Nursing, Chang Gung Institute of Technology, Taoyuan 33303, TaiwanDepartment of Physiology, National Yang-Ming University, Taipei 11221, TaiwanSoluble epoxide hydrolase (sEH) is abundantly expressed in kidney and plays a potent role in regulating inflammatory response in inflammatory diseases. However, the role of sEH in progression of chronic kidney diseases such as obstructive nephropathy is still elusive. In current study, wild-type (WT) and sEH deficient (sEH−/−) mice were subjected to the unilateral ureteral obstruction (UUO) surgery and the kidney injury was evaluated by histological examination, western blotting, and ELISA. The protein level of sEH in kidney was increased in UUO-treated mice group compared to nonobstructed group. Additionally, UUO-induced hydronephrosis, renal tubular injury, inflammation, and fibrosis were ameliorated in sEH−/− mice with the exception of glomerulosclerosis. Moreover, sEH−/− mice with UUO showed lower levels of inflammation-related and fibrosis-related protein such as monocyte chemoattractant protein-1, macrophage inflammatory protein-2, interleukin-1β (IL-1β), IL-6, inducible nitric oxide synthase, collagen 1A1, and α-actin. The levels of superoxide anion radical and hydrogen peroxide as well as NADPH oxidase activity were also decreased in UUO kidneys of sEH−/− mice compared to that observed in WT mice. Collectively, our findings suggest that sEH plays an important role in the pathogenesis of experimental obstructive nephropathy and may be a therapeutic target for the treatment of obstructive nephropathy-related diseases.http://dx.doi.org/10.1155/2015/693260
spellingShingle Chin-Wei Chiang
Hsueh-Te Lee
Der-Cherng Tarng
Ko-Lin Kuo
Li-Ching Cheng
Tzong-Shyuan Lee
Genetic Deletion of Soluble Epoxide Hydrolase Attenuates Inflammation and Fibrosis in Experimental Obstructive Nephropathy
Mediators of Inflammation
title Genetic Deletion of Soluble Epoxide Hydrolase Attenuates Inflammation and Fibrosis in Experimental Obstructive Nephropathy
title_full Genetic Deletion of Soluble Epoxide Hydrolase Attenuates Inflammation and Fibrosis in Experimental Obstructive Nephropathy
title_fullStr Genetic Deletion of Soluble Epoxide Hydrolase Attenuates Inflammation and Fibrosis in Experimental Obstructive Nephropathy
title_full_unstemmed Genetic Deletion of Soluble Epoxide Hydrolase Attenuates Inflammation and Fibrosis in Experimental Obstructive Nephropathy
title_short Genetic Deletion of Soluble Epoxide Hydrolase Attenuates Inflammation and Fibrosis in Experimental Obstructive Nephropathy
title_sort genetic deletion of soluble epoxide hydrolase attenuates inflammation and fibrosis in experimental obstructive nephropathy
url http://dx.doi.org/10.1155/2015/693260
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