Effects of gintonin on the proliferation, migration, and tube formation of human umbilical-vein endothelial cells: involvement of lysophosphatidic-acid receptors and vascular-endothelial-growth-factor signaling
Background: Ginseng extracts are known to have angiogenic effects. However, to date, only limited information is available on the molecular mechanism underlying the angiogenic effects and the main components of ginseng that exert these effects. Human umbilical-vein endothelial cells (HUVECs) are use...
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doaj-d67c0b1bb29c4d75b3eeadbc3559eba62020-11-24T23:01:09ZengElsevierJournal of Ginseng Research1226-84532016-10-0140432533310.1016/j.jgr.2015.10.002Effects of gintonin on the proliferation, migration, and tube formation of human umbilical-vein endothelial cells: involvement of lysophosphatidic-acid receptors and vascular-endothelial-growth-factor signalingSung-Hee Hwang0Byung-Hwan Lee1Sun-Hye Choi2Hyeon-Joong Kim3Kyung Jong Won4Hwan Myung Lee5Hyewon Rhim6Hyoung-Chun Kim7Seung-Yeol Nah8Department of Pharmaceutical Engineering, College of Health Sciences, Sangji University, Wonju, KoreaDepartment of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, KoreaDepartment of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, KoreaDepartment of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, KoreaDepartment of Physiology, School of Medicine, Konkuk University, Chungju, KoreaDepartment of Cosmetic Science, College of Natural Science, Hoseo University, Asan, KoreaCenter for Neuroscience, Korea Institute of Science and Technology, Seoul, KoreaNeuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, KoreaDepartment of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, KoreaBackground: Ginseng extracts are known to have angiogenic effects. However, to date, only limited information is available on the molecular mechanism underlying the angiogenic effects and the main components of ginseng that exert these effects. Human umbilical-vein endothelial cells (HUVECs) are used as an in vitro model for screening therapeutic agents that promote angiogenesis and wound healing. We recently isolated gintonin, a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand, from ginseng. LPA plays a key role in angiogenesis and wound healing. Methods: In the present study, we investigated the in vitro effects of gintonin on proliferation, migration, and tube formation of HUVECs, which express endogenous LPA1/3 receptors. Results: Gintonin stimulated proliferation and migration of HUVECs. The LPA1/3 receptor antagonist, Ki16425, short interfering RNA against LPA1 or LPA3 receptor, and the Rho kinase inhibitor, Y-27632, significantly decreased the gintonin-induced proliferation, migration, and tube formation of HUVECs, which indicates the involvement of LPA receptors and Rho kinase activation. Further, gintonin increased the release of vascular endothelial growth factors from HUVECs. The cyclooxygenase-2 inhibitor NS-398, nuclear factor kappa B inhibitor BAY11-7085, and c-Jun N-terminal kinase inhibitor SP600125 blocked the gintonin-induced migration, which shows the involvement of cyclooxygenase-2, nuclear factor kappa B, and c-Jun N-terminal kinase signaling. Conclusion: The gintonin-mediated proliferation, migration, and vascular-endothelial-growth-factor release in HUVECs via LPA-receptor activation may be one of in vitro mechanisms underlying ginseng-induced angiogenic and wound-healing effects.http://www.sciencedirect.com/science/article/pii/S1226845315001062gintoninhuman umbilical-vein endothelial cellsLPA receptorsPanax ginseng |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sung-Hee Hwang Byung-Hwan Lee Sun-Hye Choi Hyeon-Joong Kim Kyung Jong Won Hwan Myung Lee Hyewon Rhim Hyoung-Chun Kim Seung-Yeol Nah |
spellingShingle |
Sung-Hee Hwang Byung-Hwan Lee Sun-Hye Choi Hyeon-Joong Kim Kyung Jong Won Hwan Myung Lee Hyewon Rhim Hyoung-Chun Kim Seung-Yeol Nah Effects of gintonin on the proliferation, migration, and tube formation of human umbilical-vein endothelial cells: involvement of lysophosphatidic-acid receptors and vascular-endothelial-growth-factor signaling Journal of Ginseng Research gintonin human umbilical-vein endothelial cells LPA receptors Panax ginseng |
author_facet |
Sung-Hee Hwang Byung-Hwan Lee Sun-Hye Choi Hyeon-Joong Kim Kyung Jong Won Hwan Myung Lee Hyewon Rhim Hyoung-Chun Kim Seung-Yeol Nah |
author_sort |
Sung-Hee Hwang |
title |
Effects of gintonin on the proliferation, migration, and tube formation of human umbilical-vein endothelial cells: involvement of lysophosphatidic-acid receptors and vascular-endothelial-growth-factor signaling |
title_short |
Effects of gintonin on the proliferation, migration, and tube formation of human umbilical-vein endothelial cells: involvement of lysophosphatidic-acid receptors and vascular-endothelial-growth-factor signaling |
title_full |
Effects of gintonin on the proliferation, migration, and tube formation of human umbilical-vein endothelial cells: involvement of lysophosphatidic-acid receptors and vascular-endothelial-growth-factor signaling |
title_fullStr |
Effects of gintonin on the proliferation, migration, and tube formation of human umbilical-vein endothelial cells: involvement of lysophosphatidic-acid receptors and vascular-endothelial-growth-factor signaling |
title_full_unstemmed |
Effects of gintonin on the proliferation, migration, and tube formation of human umbilical-vein endothelial cells: involvement of lysophosphatidic-acid receptors and vascular-endothelial-growth-factor signaling |
title_sort |
effects of gintonin on the proliferation, migration, and tube formation of human umbilical-vein endothelial cells: involvement of lysophosphatidic-acid receptors and vascular-endothelial-growth-factor signaling |
publisher |
Elsevier |
series |
Journal of Ginseng Research |
issn |
1226-8453 |
publishDate |
2016-10-01 |
description |
Background: Ginseng extracts are known to have angiogenic effects. However, to date, only limited information is available on the molecular mechanism underlying the angiogenic effects and the main components of ginseng that exert these effects. Human umbilical-vein endothelial cells (HUVECs) are used as an in vitro model for screening therapeutic agents that promote angiogenesis and wound healing. We recently isolated gintonin, a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand, from ginseng. LPA plays a key role in angiogenesis and wound healing.
Methods: In the present study, we investigated the in vitro effects of gintonin on proliferation, migration, and tube formation of HUVECs, which express endogenous LPA1/3 receptors.
Results: Gintonin stimulated proliferation and migration of HUVECs. The LPA1/3 receptor antagonist, Ki16425, short interfering RNA against LPA1 or LPA3 receptor, and the Rho kinase inhibitor, Y-27632, significantly decreased the gintonin-induced proliferation, migration, and tube formation of HUVECs, which indicates the involvement of LPA receptors and Rho kinase activation. Further, gintonin increased the release of vascular endothelial growth factors from HUVECs. The cyclooxygenase-2 inhibitor NS-398, nuclear factor kappa B inhibitor BAY11-7085, and c-Jun N-terminal kinase inhibitor SP600125 blocked the gintonin-induced migration, which shows the involvement of cyclooxygenase-2, nuclear factor kappa B, and c-Jun N-terminal kinase signaling.
Conclusion: The gintonin-mediated proliferation, migration, and vascular-endothelial-growth-factor release in HUVECs via LPA-receptor activation may be one of in vitro mechanisms underlying ginseng-induced angiogenic and wound-healing effects. |
topic |
gintonin human umbilical-vein endothelial cells LPA receptors Panax ginseng |
url |
http://www.sciencedirect.com/science/article/pii/S1226845315001062 |
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