title: Jaceosidin, a natural flavone, promotes angiogenesis via activation of VEGFR2/FAK/PI3K/AKT/NF-κB signaling pathways in endothelial cells.
abstract: Angiogenesis, the growth of new blood vessels from pre-existing vasculature, plays an important role in physiological and pathological processes such as embryonic development wound healing and revascularization of tissues after exposure to ischemia. We investigated the effects of jaceosidin, a main constituent of medicinal herbs of the genus Artemisia, on angiogenesis and signaling pathways in endothelial cells. Jaceosidin stimulated proliferation, migration and tubulogenesis of ECs as well as ex vivo sprouting from aorta rings, which are phenomena typical of angiogenesis. Jaceosidin activated vascular endothelial growth factor receptor 2 (VEGFR2, FLk-1/KDR) and angiogenic signaling molecules such as focal adhesion kinase, phosphatidylinositol 3-kinase, and its downstream target, the serine-threonine kinase AKTWe also demonstrated that jaceosidin activated the NF-κB-driven expression of a luciferase reporter gene and NF-κB binding to DNA. Jaceosidin-induced proliferation and migration of human umbilical vascular endothelial cells were strongly inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002 and NF-κB inhibitor BAY11-7082, indicating that the PI3K/AKT/NF-κB signaling pathway is involved in jaceosidin-induced angiogenesis. Our results suggest that jaceosidin stimulates angiogenesis by activating the VEGFR2/FAK/PI3K/AKT/NF-κB signaling pathway and that it may be useful in developing angiogenic agents to promote the growth of collateral blood vessels in ischemic tissues.
authors.affiliation: Graduate School of Biotechnology and College of Life Sciences, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Lee
authors.affiliation: Graduate School of Biotechnology and College of Life Sciences, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Jung
authors.affiliation: Graduate School of Biotechnology and College of Life Sciences, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Keun Hyung
authors.initials: KH
authors.lastname: Park
authors.affiliation: Graduate School of Biotechnology and College of Life Sciences, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Myun Ho
authors.initials: MH
authors.lastname: Bang
authors.affiliation: Graduate School of Biotechnology and College of Life Sciences, Kyung Hee University, Yongin 446-701, Korea.
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Baek
authors.affiliation: Graduate School of Biotechnology and College of Life Sciences, Kyung Hee University, Yongin 446-701, Korea jkim@khu.ac.kr.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D019306:Artemisia / Q000737:chemistry; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D005419:Flavonoids / Q000302:isolation & purification / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D005419:Flavonoids; D016328:NF-kappa B; C477508:jaceosidin; D058539:Phosphatidylinositol 3-Kinase; D040301:Vascular Endothelial Growth Factor Receptor-2; D051417:Focal Adhesion Kinase 1; D051057:Proto-Oncogene Proteins c-akt
keywords: Angiogenesis; Artemisia princeps Pampanini; NF-κB; endothelial cell; jaceosidin; signaling pathway