title: Ginsenoside-Rg1 induces angiogenesis by the inverse regulation of MET tyrosine kinase receptor expression through miR-23a.
abstract: Therapeutic angiogenesis has been implicated in ischemic diseases and wound healing. Ginsenoside-Rg1 (Rg1), one of the most abundant active components of ginseng, has been demonstrated as an angiogenesis-stimulating compound in different models. There is increasing evidence implicating microRNAs (miRNAs), a group of non-coding RNAs, as important regulators of angiogenesis, but the role of microRNAs in Rg1-induced angiogenesis has not been fully explored. In this report, we found that stimulating endothelial cells with Rg1 could reduce miR-23a expression. In silico experiments predicted hepatocyte growth factor receptor (MET), a well-established mediator of angiogenesis, as the target of miR-23a. Transfection of the miR-23a precursor or inhibitor oligonucleotides validated the inverse relationship of miR-23a and MET expression. Luciferase reporter assays further confirmed the interaction between miR-23a and the MET mRNA 3'-UTR. Intriguingly, ginsenoside-Rg1 was found to increase MET protein expression in a time-dependent manner. We further demonstrated that ginsenoside-Rg1-induced angiogenic activities were indeed mediated through the down-regulation of miR-23a and subsequent up-regulation of MET protein expression, as confirmed by gain- and loss-of-function angiogenic experiments. In summary, our results demonstrated that ginsenoside-Rg1 could induce angiogenesis by the inverse regulation of MET tyrosine kinase receptor expression through miR-23a. This study has broadened our understanding of the non-genomic effects of ginsenoside-Rg1, and provided molecular evidence that warrant further development of natural compound as novel angiogenesis-promoting therapy.
authors.affiliation: Dr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Hoi-Hin
authors.initials: HH
authors.lastname: Kwok
authors.affiliation: Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Lai-Sheung
authors.initials: LS
authors.lastname: Chan
authors.affiliation: Dr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Po-Ying
authors.initials: PY
authors.lastname: Poon
authors.affiliation: Dr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR, China; Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Patrick Ying-Kit
authors.initials: PY
authors.lastname: Yue
authors.affiliation: Dr. Gilbert Hung Ginseng Laboratory, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR, China; Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR, China. Electronic address: rnswong@hkbu.edu.hk.
authors.forename: Ricky Ngok-Shun
authors.initials: RN
authors.lastname: Wong
mesh_terms: D020413:3' Untranslated Regions; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D001665:Binding Sites; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D036145:Ginsenosides / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D043925:Angiogenesis Inducing Agents; D036145:Ginsenosides; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; C035054:ginsenoside Rg1
keywords: Angiogenesis; Ginsenoside-Rg(1); Hepatocyte growth factor receptor; MET; miR-23a; microRNA