| 논문분류 | 춘계학술대회 초록집 |
|---|---|
| 제목 | Modulation of Endothelial function Attenuates Kidney Fibrosis by Regulation of Soluble Epoxide Hydrolase |
| 저자 | Jung Pyo Lee1, Seung Hee Yang3, Jin Hyuk Kim1, Do Hyung Kim4, Hee-Yoon Lee5, Joo-Youn Cho4, Yoon Kyu Oh1, Yon Su Kim2, Chun Soo Lim1 |
| 출판정보 | 2013; 2013(1): |
| 키워드 | 내피세포, 신섬유화, 에폭사이드 하이드롤라아제/ Endothelial cell, Kidney fibrosis, Soluble epoxide hydrolase |
| 초록 | Background: Soluble epoxide hydrolase (sEH) in endothelial cells catalyses the degradation of epoxyeicosatrienoic acids (EETs), which may act as vasoactive agents to control vascular tone. Kidney fibrosis is the final common pathway for most progressive kidney diseases. Here we show that kidney fibrosis was reduced by regulation of sEH activity. Methods: Unilateral ureteral obstruction (UUO) was used as a model of kidney fibrosis in C57BL/6 mice. sEH activity was controlled by continuous release of the sEH inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA) (8 mg/kg/day) for 1 or 2 wks. Results: Administration of the sEH inhibitor AUDA had no significant effect on blood pressure. AUDA treatment restored significantly improved tubulointerstital fibrosis. Fibroblast marker FSP-1 and TGFβ expressions were significantly decreased. AUDA increased the expression of endothelial markers vWF, VE-cadherin, and CD31. On flow cytometric analysis, UUO increased FSP-1 positive cell population and AUDA treatment reduced CD 31 proportion in FSP-1 postive cell. Similarly, sEH inhibition reduced vWF/FSP-1 double positive cells. In an endothelial-to-mesenchymal transition (EndMT) in-vitro model using HUVECs and in an epithelial-to-mesenchymal transition (EMT) using tubular epithelial cell (TEC), AUDA treatment restored the morphologic change and reduced the expression of FSP-1 in HUVEC but did not restore in TECs. However, AUDA-activated HUVEC significantly restored the EMT of TECs in co-culture system using the TranswellTM system. Conclusion: The results of this study suggest that direct inhibiting EndMT and indirection inhibiotion of EMT by treatment with sEH inhibitors may be an effective therapy for delaying the progression of fibrosis associated with CKD. |
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