Lysophosphatidic acid up-regulates vascular endothelial growth factor-C and lymphatic marker expressions in human endothelial cells

被引：0

作者：

C.-I. Lin

C.-N. Chen

M.-T. Huang

S.-J. Lee

C.-H. Lin

C.-C. Chang

H. Lee

机构：

[1] National Taiwan University,Institute of Zoology

[2] National Taiwan University,Department of Life Science

[3] National Taiwan University,Angiogenesis Research Center

[4] National Taiwan University Hospital,Department of Surgery

[5] National Taiwan University Hospital,Department of Pediatrics

[6] National Taiwan University,Laboratory of Molecular and Cellular Toxicology, Institute of Toxicology

[7] Academia Sinica,Division of Mechanics, Research Center for Applied Sciences

来源：

Cellular and Molecular Life Sciences | 2008年 / 65卷

关键词：

LPA; VEGF-C; endothelial cells; lymphatic markers; lymphangiogenesis;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Lysophosphatidic acid (LPA) is a low-molecular-weight lipid growth factor, which binds to G-protein-coupled receptors. Previous studies have shown that LPA enhances vascular endothelial growth factor-A (VEGF-A) expression in cancer cells and promotes angiogenesis process. However, the roles of LPA in lymphatic vessel formation and lymphangiogenesis have not been investigated. Here, we demonstrated that LPA up-regulated VEGF-C mRNA and protein expressions in human umbilical vein endothelial cells (HUVECs). Furthermore, the expression levels of lymphatic markers, including Prox-1, LYVE-1 and podoplanin, were enhanced in LPA-stimulated tube forming endothelial cells in vitro and in vivo. Moreover, we showed that pretreatment with MAZ51, a VEGFR-3 kinase inhibitor, and introduction of VEGFR-3 siRNA suppressed LPA-induced HUVEC tube formation and lymphatic marker expressions. These results demonstrated that LPA enhances expression of lymphatic markers through activating VEGF-C receptors in endothelial cells. This study provides basic information that LPA might be a target for therapeutics against lymphangiogenesis and tumor metastasis.

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