Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway
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摘要Formononetin is an isoflavone that has been shown to display estrogenic properties and induce angiogenesis activities. However, the interrelationship between the estrogenic properties and angiogenesis activities of formononetin are not well defined. In the present study, docking and enzymatic assay demonstrated that formononetin displayed direct binding to the ligand-binding domain (LBD) of estrogen receptor alpha (ER alpha) with an agonistic property. Results from Human Umbilical Vein Endothelial Cells (HUVEC) by using real-time migration xCELLigence system, immunofluorescence and western blotting provided strong evidences of formononetin induced endothelial cell migration and dramatic actin cytoskeleton spatial modification through ER alpha-enhanced- ROCK-II/MMP2/9 signaling pathways. In addition, results from co-immunoprecipitation suggested formononetin induced cell migration via recruiting of ER alpha/ROCK-II activated complex formation. More interestingly, in zebrafish embryo we observed that formononetin significantly promoted angiogenic sproutings in the subintestinal vessels (SIVs) that could be completely abolished by ROCK inhibitor. In this study, we elucidated the underlying mechanisms that formononetin produced proangiogenesis effects through an ER alpha-enhanced ROCK-II signaling pathways. Results from the present study also expand our knowledge about the enigmatic underlying mechanisms of phytoestrogenic compounds in the promotion of angiogenesis in relation to ERa and ROCK interaction in endothelial cells and their relationship with actin assembly and cell migration.
著者Li S, Dang YY, Zhou XL, Huang B, Huang XH, Zhang ZR, Kwan YW, Chan SW, Leung GPH, Lee SMY, Hoi MPM
期刊名稱Scientific Reports
出版年份2015
月份11
日期16
卷號5
出版社NATURE PUBLISHING GROUP
國際標準期刊號2045-2322
電子國際標準期刊號2045-2322
語言英式英語
Web of Science 學科類別Multidisciplinary Sciences; Science & Technology - Other Topics

上次更新時間 2020-14-09 於 02:20