Kidney Res Clin Pract.
2017 Dec;36(4):329-341. 10.23876/j.krcp.2017.36.4.329.
Active maintenance of endothelial cells prevents kidney fibrosis
- Affiliations
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- 1Kidney Research Institute, Seoul National University Hospital, Seoul, Korea.
- 2Seoul National University Biomedical Research Institute, Seoul, Korea.
- 3Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
- 4Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea. nephrolee@gmail.com
- 5Department of Chemistry, College of the Literature, Science and the Arts, University of Michigan, Ann Arbor, MI, USA.
- 6Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
- 7Department of Clinical Pharmacology, Seoul National University College of Medicine, Seoul, Korea.
- 8Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
- 9Department of Medical Science, Seoul National University College of Medicine, Seoul, Korea.
- 10Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
- KMID: 2405108
- DOI: http://doi.org/10.23876/j.krcp.2017.36.4.329
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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