Ginsenoside Rg3 protects against iE-DAP-induced endothelial-to-mesenchymal transition by regulating the miR-139-5p-NF-kappa B axisopen access
- Lee, Aram; Yun, Eunsik; Chang, Woochul; Kim, Jongmin
- Issue Date
- KOREAN SOC GINSENG
- endothelial-to-mesenchymal transition; ginsenoside Rg3; iE-DAP; inflammation; microRNA
- JOURNAL OF GINSENG RESEARCH, v.44, no.2, pp.300 - 307
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- JOURNAL OF GINSENG RESEARCH
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- Background: Emerging evidence suggests that endothelial-to-mesenchymal transition (EndMT) in endothelial dysfunction due to persistent inflammation is a key component and emerging concept in the pathogenesis of vascular diseases. Ginsenoside Rg3 (Rg3), an active compound from red ginseng, has been known to be important for vascular homeostasis. However, the effect of Rg3 on inflammation-induced EndMT has never been reported. Here, we hypothesize that Rg3 might reverse the inflammation-induced EndMT and serve as a novel therapeutic strategy for vascular diseases. Methods: EndMT was examined under an inflammatory condition mediated by the NOD1 agonist, gamma-d-glutamyl-meso-diaminopimelic acid (iE-DAP), treatment in human umbilical vein endothelial cells. The expression of EndMT markers was determined by Western blot analysis, real-time polymerase chain reaction, and immunocytochemistry. The underlying mechanisms of Rg3-mediated EndMT regulation were investigated by modulating the microRNA expression. Results: The NOD1 agonist, iE-DAP, led to a fibroblast-like morphology change with a decrease in the expression of endothelial markers and an increase in the expression of the mesenchymal marker, namely EndMT. On the other hand, Rg3 markedly attenuated the iE-DAP-induced EndMT and preserved the endothelial phenotype. Mechanically, miR-139 was downregulated in cells with iE-DAP-induced EndMT and partly reversed in response to Rg3 via the regulation of NF-kappa B signaling, suggesting that the Rg3 -miR-139-5p-NF-kappa B axis is a key mediator in iE-DAP-induced EndMT. Conclusion: These results suggest, for the first time, that Rg3 can be used to inhibit inflammation-induced EndMT and may be a novel therapeutic option against EndMT-associated vascular diseases. (C) 2019 The Korean Society of Ginseng, Published by Elsevier Korea LLC.
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