Document Type

Journal Article

Department/Unit

Department of Biology

Title

Ginsenoside-Rg1 induces angiogenesis by the inverse regulation of MET tyrosine kinase receptor expression through miR-23a

Language

English

Abstract

© 2015 Elsevier Inc. 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.

Keywords

Angiogenesis, Ginsenoside-Rg1, Hepatocyte growth factor receptor, MET, MicroRNA, MiR-23a

Publication Date

2015

Source Publication Title

Toxicology and Applied Pharmacology

Volume

287

Issue

3

Start Page

276

End Page

283

Publisher

Elsevier

DOI

10.1016/j.taap.2015.06.014

Link to Publisher's Edition

http://dx.doi.org/10.1016/j.taap.2015.06.014

ISSN (print)

0041008X

ISSN (electronic)

10960333

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