title: Curculigoside A induces angiogenesis through VCAM-1/Egr-3/CREB/VEGF signaling pathway.
abstract: Curculigoside A may be a powerful way of protecting the brain against a wide variety of injury. In the present study, we sought to elucidate whether Curculigoside A contributes to induce angiogenesis and its mechanisms. To this end, we examined the role of Curculigoside A on proliferation, invasion, and tube formation in the human brain microvascular endothelial cell line (HBMEC) in vitro. For studying mechanism, the cAMP response element-binding protein (CREB) inhibitor 2-naphthol-AS-E-phosphate (KG-501), early growth response 3 (Egr-3) siRNA, vascular endothelial growth factor (VEGF) antagonist sFlt-1 and VEGF receptor 2 (VEGFR2) blocker SU-1498 were used. Human brain microvascular endothelial cell line (HMBEC) proliferation was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Scratch adhesion test was used to assess the ability of invasion. A matrigel tube formation assay was performed to test capillary tube formation ability. Vascular cell adhesion molecule 1 (VCAM-1)/Egr-3/CREB/VEGF pathway activation in HMBEC was tested by Western blot analysis. Our data suggested that Curculigoside A induced angiogenesis in vitro by enhancing the proliferation, invasion and tube formation. VEGF expression was increased by Curculigoside A and counteracted by the soluble VEGF receptor 1 (sFlt-1, VEGF antagonist) and KG-501 in HMBEC. Tube formation was enhanced by Curculigoside A and counteracted by VEGF receptor blocker-SU1498, KG-501 and Egr-3 siRNA. It may be suggested that Curculigoside A induces angiogenesis in vitro via a programed VCAM-1/Egr-3/CREB/VEGF signaling axis.
authors.affiliation: School of Pharmaceutical Sciences and Institute of Material Medica, Binzhou Medical University, Yantai 264003, PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Kang
authors.affiliation: State Key Laboratory of Long-acting and Targeting Drug Delivery Technologies (Luye Pharma Group Limited), Yantai 264003, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences and Institute of Material Medica, Binzhou Medical University, Yantai 264003, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Luan
authors.affiliation: School of Pharmaceutical Sciences and Institute of Material Medica, Binzhou Medical University, Yantai 264003, PR China.
authors.forename: F
authors.initials: F
authors.lastname: Han
authors.affiliation: School of Pharmaceutical Sciences and Institute of Material Medica, Binzhou Medical University, Yantai 264003, PR China. Electronic address: jwl518@163.com.
authors.forename: W
authors.initials: W
authors.lastname: Jiang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001565:Benzoates / Q000633:toxicity*; D001921:Brain / Q000166:cytology; D050882:CREB-Binding Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D005947:Glucose / Q000172:deficiency; D005960:Glucosides / Q000633:toxicity*; D006801:Humans; D000860:Hypoxia / Q000473:pathology; D055806:Microvessels / Q000166:cytology; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D001565:Benzoates; D051638:Ether-A-Go-Go Potassium Channels; D005960:Glucosides; C486376:KCNH7 protein, human; C467484:VEGFA protein, human; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C477170:curculigoside; D050882:CREB-Binding Protein; D053148:Caspase 3; D005947:Glucose
keywords: CREB; Curculigoside A; Egr-3; VCAM-1; VEGF; angiogenesis