Active maintenance of endothelial cells prevents kidney fibrosis
Kidney Research and Clinical Practice
;
: 329-341, 2017.
Artigo
em Inglês
| WPRIM
| ID: wpr-143311
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Obstrução Ureteral
/
Técnicas In Vitro
/
Fibrose
/
Técnicas de Cocultura
/
Células Endoteliais
/
Células Epiteliais
/
Insuficiência Renal Crônica
/
Transição Epitelial-Mesenquimal
/
Fibroblastos
/
Rim
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Kidney Research and Clinical Practice
Ano de publicação:
2017
Tipo de documento:
Artigo
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