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논문분류 춘계학술대회 초록집
제목 N-3-oxododecanoyl homoserine lactone inhibits angiogenesis by activating the angiopoietin-Tie system in human endothelial cells
저자 Jungho Shin,Sun Hee Ahn,Su Hyun Kim,Dong-Jin Oh
출판정보 2022; 2022(1):
키워드
초록 Objectives: The dysregulation of the angiopoietin-Tie system is associated with the development of sepsis-associated endothelial dysfunction. Bacterial quorum-sensing molecules act as pathogen-associated molecular patterns, however, the effect of quorum-sensing molecules on the angiopoietin-Tie system remains uncertain. Methods: This study investigated the molecular mechanisms of endothelial dysfunction in human umbilical vein endothelial cells treated with N-3-oxododecanoyl homoserine lactone (3OC12-HSL) derived from Pseudomonas aeruginosa. Results: Treatment with 3OC12-HSL reduced cell viability in a dose-dependent manner. Moreover, 3OC12-HSL treatment impaired the ability of tube formation even at non-lethal concentrations. The patterns of mRNA expression regarding the angiopoietin-Tie axis were assessed and the increased mRNA expressions of angiopoietin-2, Foxo-1, Tie1, and VEGFR2 were found in the 3OC12-HSL-treated cells. Western blot revealed that treatment with 3OC12-HSL increased the relative expressions of agiopoietin-2 and Foxo-1 and decreased the expression of Tie2. The study further evaluated the expression of IQGAP1 and the expressions of IQGAP1 and Rac1 decreased in cells treated with 3OC12-HSL. In addition, coimmunoprecipitation studies showed that treatment with 3OC12-HSL decreased the association between IQGAP1 and Rac1 in endothelial cells. Conclusions: 3OC12-HSL can impair endothelial angiogenesis via the activation of the angiopoietin-Tie pathway. In addition, it may induce the dissociation of IQGAP1 with Rac1. Adjuvant therapy for blocking the quorum-sensing systems can help preserve endothelial cell integrity and prevent organ failure in patients with sepsis.
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