title: MicroRNA-15b contributes to ginsenoside-Rg1-induced angiogenesis through increased expression of VEGFR-2.
abstract: Ginsenoside-Rg1 (Rg1) has been identified as potent proangiogenic agent, which plays an important role in wound healing promotion or treatment of ischemic injury. We previously reported that miR-214/eNOS pathway was involved in Rg1-induced angiogenesis. Following the same microRNA microarray profiling data, we proposed miR-15b would be another microRNA candidate involved in Rg1-induced angiogenesis. Using human umbilical vein endothelial cells (HUVECs), it was showed that Rg1 could reduce miR-15b expression rapidly and steadily, leading to a temporal induction of vascular endothelial growth factor receptor-2 (VEGFR-2). The in vitro motility and tubulogenesis via VEGFR-2 in Rg1-treated HUVECs were also demonstrated. Besides, the reduction of VEGFR-2 3'-UTR reporter activity by miR-15b in the luciferase reporter gene assay clearly indicated that miR-15b could affect the VEGFR-2 transcript through targeting its 3'-UTR region. Diminishing expression of endogenous miR-15b could increase VEGFR-2 expression and HUVECs migration and tubulogenesis; while over-expression of miR-15b was found to associate with the reduction of VEGFR-2 expression as well as cellular migration and tubulogenesis. In vivo, artificial increment of miR-15b by injecting Pre-miR-15b precursor into zebrafish embryos was also found to significantly suppress the subintestinal vessels formation. In conclusion, our results further demonstrated the involvement of microRNAs in Rg1-induced angiogenesis.
authors.affiliation: Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong.
authors.forename: L S
authors.initials: LS
authors.lastname: Chan
authors.forename: Patrick Y K
authors.initials: PY
authors.lastname: Yue
authors.forename: Y Y
authors.initials: YY
authors.lastname: Wong
authors.forename: Ricky N S
authors.initials: RN
authors.lastname: Wong
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D036145:Ginsenosides / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis*; D015027:Zebrafish
chemical_list: D043925:Angiogenesis Inducing Agents; D036145:Ginsenosides; C505361:MIRN15 microRNA, human; D035683:MicroRNAs; D040301:Vascular Endothelial Growth Factor Receptor-2; C035054:ginsenoside Rg1
keywords: Angiogenesis; Ginsenoside-Rg(1); HUVECs; Microrna-15b; VEGFR-2