Active maintenance of endothelial cells prevents kidney fibrosis
Kidney Research and Clinical Practice
;
: 329-341, 2017.
Article
in English
| WPRIM
| ID: wpr-143318
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Ureteral Obstruction
/
In Vitro Techniques
/
Fibrosis
/
Coculture Techniques
/
Endothelial Cells
/
Epithelial Cells
/
Renal Insufficiency, Chronic
/
Epithelial-Mesenchymal Transition
/
Fibroblasts
/
Kidney
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Kidney Research and Clinical Practice
Year:
2017
Type:
Article
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