PUBLICATION
Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway
- Authors
- Li, S., Dang, Y., Zhou, X., Huang, B., Huang, X., Zhang, Z., Kwan, Y.W., Chan, S.W., Leung, G.P., Lee, S.M., Hoi, M.P.
- ID
- ZDB-PUB-151117-8
- Date
- 2015
- Source
- Scientific Reports 5: 16815 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Human Umbilical Vein Endothelial Cells
- Protein Structure, Tertiary
- Estrogen Receptor alpha/antagonists & inhibitors
- Estrogen Receptor alpha/genetics
- Estrogen Receptor alpha/metabolism*
- Neovascularization, Physiologic/drug effects*
- Estradiol/analogs & derivatives
- Estradiol/pharmacology
- Humans
- Isoflavones/chemistry
- Isoflavones/metabolism
- Isoflavones/pharmacology*
- Signal Transduction/drug effects*
- RNA Interference
- Cell Movement/drug effects
- Binding Sites
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Zebrafish
- Matrix Metalloproteinase 9/metabolism
- Actin Cytoskeleton/drug effects
- Actin Cytoskeleton/metabolism
- Animals
- Matrix Metalloproteinase 2/metabolism
- Molecular Docking Simulation
- Vascular Endothelial Growth Factor A/pharmacology
- rho-Associated Kinases/antagonists & inhibitors
- rho-Associated Kinases/genetics
- rho-Associated Kinases/metabolism*
- PubMed
- 26568398 Full text @ Sci. Rep.
Citation
Li, S., Dang, Y., Zhou, X., Huang, B., Huang, X., Zhang, Z., Kwan, Y.W., Chan, S.W., Leung, G.P., Lee, S.M., Hoi, M.P. (2015) Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway. Scientific Reports. 5:16815.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping