Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway
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AbstractFormononetin 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.
All Author(s) ListLi S, Dang YY, Zhou XL, Huang B, Huang XH, Zhang ZR, Kwan YW, Chan SW, Leung GPH, Lee SMY, Hoi MPM
Journal nameScientific Reports
Year2015
Month11
Day16
Volume Number5
PublisherNATURE PUBLISHING GROUP
ISSN2045-2322
eISSN2045-2322
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesMultidisciplinary Sciences; Science & Technology - Other Topics

Last updated on 2020-21-05 at 02:30