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KMID : 1102220170360040329
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Kidney Research and Clinical Practice
2017 Volume.36 No. 4 p.329 ~ p.341
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Active maintenance of endothelial cells prevents kidney fibrosis
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Yang Seung-Hee
Kim Yong-Chul
An Jung-Nam
Kim Jin-Hyuk
Lee Juh-Oh
Lee Hee-Yoon
Cho Joo-Youn
Paik Jin-Ho
Oh Yun-Kyu
Lim Chun-Soo
Kim Yon-Su
Lee Jung-Pyo
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Abstract
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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.
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KEYWORD
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Epithelial-mesenchymal transition, Endothelial dysfunction, Endothelial-to-mesenchymal transition, Kidney fibrosis, Soluble epoxide hydrolase
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