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

被引：33

作者：

Lin, C. -I. ^{[1
]}

Chen, C. -N. ^{[3
,4
,7
]}

Huang, M. -T. ^{[5
]}

Lee, S. -J. ^{[1
,2
]}

Lin, C. -H. ^{[1
]}

Chang, C. -C. ^{[6
]}

Lee, H. ^{[1
,2
,3
,4
]}

机构：

[1] Natl Taiwan Univ, Inst Zool, Taipei 106, Taiwan

[2] Natl Taiwan Univ, Dept Life Sci, Taipei 10764, Taiwan

[3] Natl Taiwan Univ, Angiogenesis Res Ctr, Taipei 10764, Taiwan

[4] Natl Taiwan Univ Hosp, Dept Surg, Taipei 100, Taiwan

[5] Natl Taiwan Univ Hosp, Dept Pediat, Taipei 100, Taiwan

[6] Natl Taiwan Univ, Lab Mol & Cellular Toxicol, Inst Toxicol, Taipei 10764, Taiwan

[7] Acad Sinica, Div Mech, Res Ctr Appl Sci, Taipei 115, Taiwan

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2008年 / 65卷 / 17期

关键词：

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

D O I：

10.1007/s00018-008-8314-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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.

引用

页码：2740 / 2751

页数：12

共 51 条

[1] Lysophosphatidic acid up-regulates expression of interleukin-8 and-6 in granulosa-lutein cells through its receptors and nuclear factor-κB dependent pathways:: Implications for angiogenesis of corpus luteum and ovarian hyperstimulation syndrome [J].