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Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway
Li S.4; Dang Y.4; Zhou X.1; Huang B.4; Huang X.4; Zhang Z.4; Kwan Y.W.1; Chan S.W.2; Leung G.P.H.3; Lee S.M.Y.4; Hoi M.P.M.4
Source PublicationScientific Reports

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 (ERα) 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 ERα-enhanced-ROCK-II/MMP2/9 signaling pathways. In addition, results from co-immunoprecipitation suggested formononetin induced cell migration via recruiting of ERα/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 ERα-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 ERα and ROCK interaction in endothelial cells and their relationship with actin assembly and cell migration.

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Indexed BySCI
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000364662800001
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Cited Times [WOS]:20   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Chinese University of Hong Kong
2.Hong Kong Polytechnic University
3.The University of Hong Kong
4.University of Macau
First Author AffilicationUniversity of Macau
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GB/T 7714
Li S.,Dang Y.,Zhou X.,et al. Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway[J]. Scientific Reports,2015,5.
APA Li S..,Dang Y..,Zhou X..,Huang B..,Huang X..,...&Hoi M.P.M..(2015).Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway.Scientific Reports,5.
MLA Li S.,et al."Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway".Scientific Reports 5(2015).
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