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Article: Calycosin promotes angiogenesis involving estrogen receptor and mitogen-activated protein kinase (MAPK) signaling pathway in zebrafish and HUVEC

TitleCalycosin promotes angiogenesis involving estrogen receptor and mitogen-activated protein kinase (MAPK) signaling pathway in zebrafish and HUVEC
Authors
Issue Date2010
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2010, v. 5 n. 7 How to Cite?
AbstractBackground: Angiogenesis plays an important role in a wide range of physiological processes, and many diseases are associated with the dysregulation of angiogenesis. Radix Astragali is a Chinese medicinal herb commonly used for treating cardiovascular disorders and has been shown to possess angiogenic effect in previous studies but its active constituent and underlying mechanism remain unclear. The present study investigates the angiogenic effects of calycosin, a major isoflavonoid isolated from Radix Astragali, in vitro and in vivo.Methodology: Tg(fli1:EGFP) and Tg(fli1:nEGFP) transgenic zebrafish embryos were treated with different concentrations of calycosin (10, 30, 100 μM) from 72 hpf to 96 hpf prior morphological observation and angiogenesis phenotypes assessment. Zebrafish embryos were exposed to calycosin (10, 100 μM) from 72 hpf to 78 hpf before gene-expression analysis. The effects of VEGFR tyrosine kinase inhibitor on calycosin-induced angiogenesis were studied using 72 hpf Tg(fli1:EGFP) and Tg(fli1:nEGFP) zebrafish embryos. The pro-angiogenic effects of calycosin were compared with raloxifene and tamoxifen in 72 hpf Tg(fli1:EGFP) zebrafish embryos. The binding affinities of calycosin to estrogen receptors (ERs) were evaluated by cell-free and cell-based estrogen receptor binding assays. Human umbilical vein endothelial cell cultures (HUVEC) were pretreated with different concentrations of calycosin (3, 10, 30, 100 mM) for 48 h then tested for cell viability and tube formation. The role of MAPK signaling in calycosin-induced angiogenesis was evaluated using western blotting. Conclusion: Calycosin was shown to induce angiogenesis in human umbilical vein endothelial cell cultures (HUVEC) in vitro and zebrafish embryos in vivo via the up-regulation of vascular endothelial growth factor (VEGF), VEGFR1 and VEGFR2 mRNA expression. It was demonstrated that calycosin acted similar to other selective estrogen receptor modulators (SERMs), such as raloxifene and tamoxifen, by displaying selective potency and affinity to estrogen receptors ERa and ERb. Our results further indicated that calycosin promotes angiogenesis via activation of MAPK with the involvement of ERK1/2 and ER. Together, this study revealed, for the first time, that calycosin acts as a selective estrogen receptor modulator (SERM) to promote angiogenesis, at least in part through VEGF-VEGFR2 and MAPK signaling pathways. © 2010 Tang et al.
Persistent Identifierhttp://hdl.handle.net/10722/137486
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Science and Technology Development Fund of Macau SAR045/2007/A3
Research Committee, University of MacauRG085
UL017/09-Y1
Funding Information:

This study is supported by grant from the Science and Technology Development Fund of Macau SAR (Ref. No. 045/2007/A3) and Research Committee, University of Macau (Ref. No. RG085 and UL017/09-Y1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorTang, JYen_HK
dc.contributor.authorLi, Sen_HK
dc.contributor.authorLi, ZHen_HK
dc.contributor.authorZhang, ZJen_HK
dc.contributor.authorHu, Gen_HK
dc.contributor.authorCheang, LCVen_HK
dc.contributor.authorAlex, Den_HK
dc.contributor.authorHoi, MPMen_HK
dc.contributor.authorKwan, YWen_HK
dc.contributor.authorChan, SWen_HK
dc.contributor.authorLeung, GPHen_HK
dc.contributor.authorLee, SMYen_HK
dc.date.accessioned2011-08-26T14:26:05Z-
dc.date.available2011-08-26T14:26:05Z-
dc.date.issued2010en_HK
dc.identifier.citationPlos One, 2010, v. 5 n. 7en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137486-
dc.description.abstractBackground: Angiogenesis plays an important role in a wide range of physiological processes, and many diseases are associated with the dysregulation of angiogenesis. Radix Astragali is a Chinese medicinal herb commonly used for treating cardiovascular disorders and has been shown to possess angiogenic effect in previous studies but its active constituent and underlying mechanism remain unclear. The present study investigates the angiogenic effects of calycosin, a major isoflavonoid isolated from Radix Astragali, in vitro and in vivo.Methodology: Tg(fli1:EGFP) and Tg(fli1:nEGFP) transgenic zebrafish embryos were treated with different concentrations of calycosin (10, 30, 100 μM) from 72 hpf to 96 hpf prior morphological observation and angiogenesis phenotypes assessment. Zebrafish embryos were exposed to calycosin (10, 100 μM) from 72 hpf to 78 hpf before gene-expression analysis. The effects of VEGFR tyrosine kinase inhibitor on calycosin-induced angiogenesis were studied using 72 hpf Tg(fli1:EGFP) and Tg(fli1:nEGFP) zebrafish embryos. The pro-angiogenic effects of calycosin were compared with raloxifene and tamoxifen in 72 hpf Tg(fli1:EGFP) zebrafish embryos. The binding affinities of calycosin to estrogen receptors (ERs) were evaluated by cell-free and cell-based estrogen receptor binding assays. Human umbilical vein endothelial cell cultures (HUVEC) were pretreated with different concentrations of calycosin (3, 10, 30, 100 mM) for 48 h then tested for cell viability and tube formation. The role of MAPK signaling in calycosin-induced angiogenesis was evaluated using western blotting. Conclusion: Calycosin was shown to induce angiogenesis in human umbilical vein endothelial cell cultures (HUVEC) in vitro and zebrafish embryos in vivo via the up-regulation of vascular endothelial growth factor (VEGF), VEGFR1 and VEGFR2 mRNA expression. It was demonstrated that calycosin acted similar to other selective estrogen receptor modulators (SERMs), such as raloxifene and tamoxifen, by displaying selective potency and affinity to estrogen receptors ERa and ERb. Our results further indicated that calycosin promotes angiogenesis via activation of MAPK with the involvement of ERK1/2 and ER. Together, this study revealed, for the first time, that calycosin acts as a selective estrogen receptor modulator (SERM) to promote angiogenesis, at least in part through VEGF-VEGFR2 and MAPK signaling pathways. © 2010 Tang et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshEndothelial Cells - cytology - metabolism-
dc.subject.meshIsoflavones - genetics - metabolism-
dc.subject.meshMitogen-Activated Protein Kinases - genetics - metabolism-
dc.subject.meshNeovascularization, Physiologic - genetics - physiology-
dc.subject.meshReceptors, Estrogen - genetics - metabolism-
dc.titleCalycosin promotes angiogenesis involving estrogen receptor and mitogen-activated protein kinase (MAPK) signaling pathway in zebrafish and HUVECen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, GPH: gphleung@hkucc.hku.hken_HK
dc.identifier.authorityLeung, GPH=rp00234en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0011822en_HK
dc.identifier.pmid20686605-
dc.identifier.pmcidPMC2912279-
dc.identifier.scopuseid_2-s2.0-77955591123en_HK
dc.identifier.hkuros189205en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77955591123&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume5en_HK
dc.identifier.issue7en_HK
dc.identifier.spagee11822en_US
dc.identifier.epagee11822en_US
dc.identifier.isiWOS:000280520200007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTang, JY=13907115100en_HK
dc.identifier.scopusauthoridLi, S=36627361600en_HK
dc.identifier.scopusauthoridLi, ZH=8439008600en_HK
dc.identifier.scopusauthoridZhang, ZJ=35742521800en_HK
dc.identifier.scopusauthoridHu, G=7401490019en_HK
dc.identifier.scopusauthoridCheang, LCV=25930275700en_HK
dc.identifier.scopusauthoridAlex, D=8270038300en_HK
dc.identifier.scopusauthoridHoi, MPM=36607867300en_HK
dc.identifier.scopusauthoridKwan, YW=7005662153en_HK
dc.identifier.scopusauthoridChan, SW=7404255670en_HK
dc.identifier.scopusauthoridLeung, GPH=35963668200en_HK
dc.identifier.scopusauthoridLee, SMY=35233892600en_HK

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