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Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway
Shang Li4; Yuanye Dang4; Xuelin Zhou1; Bin Huang4; Xiaohui Huang4; Zherui Zhang4; Yiu Wa Kwan1; Shun Wan Chan2; George Pak Heng Leung3; Simon Ming Yuen Lee4; Maggie Pui Man Hoi4
2015-11-16
Source PublicationScientific Reports
ISSN20452322
Volume5
Abstract

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.

DOI10.1038/srep16815
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000364662800001
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Cited Times [WOS]:28   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
2.Department of Applied Biology and Chemical Technology, State Key Laboratory of Chinese Medicine and Molecular Pharmacology, The Hong Kong Polytechnic University, Hong Kong, China
3.Department of Applied Biology and Chemical Technology, State Key Laboratory of Chinese Medicine and Molecular Pharmacology, The Hong Kong Polytechnic University, Hong Kong, China
4.State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Shang Li,Yuanye Dang,Xuelin Zhou,et al. Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway[J]. Scientific Reports,2015,5.
APA Shang Li.,Yuanye Dang.,Xuelin Zhou.,Bin Huang.,Xiaohui Huang.,...&Maggie Pui Man Hoi.(2015).Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway.Scientific Reports,5.
MLA Shang Li,et al."Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway".Scientific Reports 5(2015).
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