Active maintenance of endothelial cells prevents kidney fibrosis

Kidney Research and Clinical Practice

Juhoh Lee¹  Hee-Yoon Lee²  Joo-Youn Cho³  Jung Pyo Lee⁴  Jung Nam An⁴  Yun Kyu Oh⁴  Chun Soo Lim⁴  Yong Chul Kim⁵  Jin Ho Paik⁶  Jin Hyuk Kim⁷  Seung Hee Yang⁷  Yon Su Kim⁷ 

[1] Department of Chemistry, College of the Literature, Science and the Arts, University of Michigan, Ann Arbor, MI, USA;Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, Korea;Department of Clinical Pharmacology, Seoul National University College of Medicine, Seoul, Korea;Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea;Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea;Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea;Kidney Research Institute, Seoul National University Hospital, Seoul, Korea;

关键词: Epithelial-mesenchymal transition;    Endothelial dysfunction;    Endothelial-to-mesenchymal transition;    Kidney fibrosis;    Soluble epoxide hydrolase;   

DOI  :  10.23876/j.krcp.2017.36.4.329

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown