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Active maintenance of endothelial cells prevents kidney fibrosis
Article de En | WPRIM | ID: wpr-143311
Bibliothèque responsable: 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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Mots clés
Texte intégral: 1 Indice: WPRIM Sujet Principal: Obstruction urétérale / Techniques in vitro / Fibrose / Techniques de coculture / Cellules endothéliales / Cellules épithéliales / Insuffisance rénale chronique / Transition épithélio-mésenchymateuse / Fibroblastes / Rein Limites du sujet: Animals / Humans langue: En Texte intégral: Kidney Research and Clinical Practice Année: 2017 Type: Article
Texte intégral: 1 Indice: WPRIM Sujet Principal: Obstruction urétérale / Techniques in vitro / Fibrose / Techniques de coculture / Cellules endothéliales / Cellules épithéliales / Insuffisance rénale chronique / Transition épithélio-mésenchymateuse / Fibroblastes / Rein Limites du sujet: Animals / Humans langue: En Texte intégral: Kidney Research and Clinical Practice Année: 2017 Type: Article