Active maintenance of endothelial cells prevents kidney fibrosis
Kidney Research and Clinical Practice
; : 329-341, 2017.
Article
em En
| WPRIM
| ID: wpr-143311
Biblioteca responsável:
WPRO
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.
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Texto completo:
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Base de dados:
WPRIM
Assunto principal:
Obstrução Ureteral
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Técnicas In Vitro
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Fibrose
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Técnicas de Cocultura
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Células Endoteliais
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Células Epiteliais
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Insuficiência Renal Crônica
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Transição Epitelial-Mesenquimal
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Fibroblastos
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Rim
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article