Active maintenance of endothelial cells prevents kidney fibrosis.
10.23876/j.krcp.2017.36.4.329
- Author:
Seung Hee YANG
1
;
Yong Chul KIM
;
Jung Nam AN
;
Jin Hyuk KIM
;
Juhoh LEE
;
Hee Yoon LEE
;
Joo Youn CHO
;
Jin Ho PAIK
;
Yun Kyu OH
;
Chun Soo LIM
;
Yon Su KIM
;
Jung Pyo LEE
Author Information
1. Kidney Research Institute, Seoul National University Hospital, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Epithelial-mesenchymal transition;
Endothelial dysfunction;
Endothelial-to-mesenchymal transition;
Kidney fibrosis;
Soluble epoxide hydrolase
- MeSH:
Animals;
Coculture Techniques;
Endothelial Cells*;
Epithelial Cells;
Epithelial-Mesenchymal Transition;
Fibroblasts;
Fibrosis*;
Humans;
In Vitro Techniques;
Kidney*;
Metabolism;
Mice;
Renal Insufficiency, Chronic;
Ureteral Obstruction
- From:Kidney Research and Clinical Practice
2017;36(4):329-341
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Soluble epoxide hydrolase (sEH) expressed by endothelial cells catalyzes the metabolism of epoxyeicosatrienoic acids (EETs), which are vasoactive agents. METHODS: We used a unilateral ureteral obstruction mouse model of kidney fibrosis to determine whether inhibition of sEH activity reduces fibrosis, the final common pathway for chronic kidney disease. RESULTS: sEH activity was inhibited by continuous release of the inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA) for 1 or 2 weeks. Treatment with AUDA significantly ameliorated tubulointerstitial fibrosis by reducing fibroblast mobilization and enhancing endothelial cell activity. In an in vitro model of endothelial-to-mesenchymal transition (EndMT) using human vascular endothelial cells (HUVECs), AUDA prevented the morphologic changes associated with EndMT and reduced expression of fibroblast-specific protein 1. Furthermore, HUVECs activated by AUDA prevented the epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells in a co-culture system. CONCLUSION: Our findings suggest that regulation of sEH is a potential target for therapies aimed at delaying the progression of kidney fibrosis by inhibiting EndMT and EMT.
