Sphingosine-1-phosphate induces VEGF-C expression through a MMP-2/FGF-1/FGFR1-dependent pathway in endothelial cells in vitro

被引：20

作者：

Chang, Chi-hao ^{[1
]}

Huang, Yuan-li ^{[2
]}

Shyu, Ming-kwang ^{[3
]}

Chen, Shee-uan ^{[3
]}

Lin, Chih-hsin ^{[1
]}

Ju, Tsai-kai ^{[4
,5
]}

Lu, JenHer ^{[6
]}

Lee, Hsinyu ^{[1
,7
,8
,9
,10
]}

机构：

[1] Natl Taiwan Univ, Inst Zool, Taipei 10764, Taiwan

[2] Asia Univ, Dept Biotechnol, Taichung, Taiwan

[3] Natl Taiwan Univ Hosp, Dept Obstet & Gynecol, Taipei, Taiwan

[4] Natl Taiwan Univ, Instrumentat Ctr, Taipei 10764, Taiwan

[5] Natl Taiwan Univ, Coll Life Sci, Taipei 10764, Taiwan

[6] Natl Yang Ming Univ, Vet Gen Hosp Taipei, Dept Pediat & Pediat Cardiol, Taipei 112, Taiwan

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

[8] Natl Taiwan Univ, Ctr Biotechnol, Taipei 10764, Taiwan

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

[10] Natl Taiwan Univ, Res Ctr Dev Biol & Regenerat Med, Taipei 10764, Taiwan

来源：

ACTA PHARMACOLOGICA SINICA | 2013年 / 34卷 / 03期

关键词：

sphingosine-1-phosphate; VEGF-C; matrix metalloproteinase-2; fibroblast growth factor-1; fibroblast growth factor receptor-1; GM6001; SU5402; transactivation; human umbilical vein endothelial cells; RNA interference; FIBROBLAST-GROWTH-FACTOR; MATRIX METALLOPROTEINASES; SPHINGOSINE; 1-PHOSPHATE; EXTRACELLULAR-MATRIX; ANGIOGENESIS; LYMPHANGIOGENESIS; TRANSACTIVATION; INHIBITION; MECHANISMS; RECEPTORS;

D O I：

10.1038/aps.2012.186

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

Aim: To investigate whether sphingosine-1-phosphate (SIP), a potent angiogenic factor, induced vascular endothelial growth factor-C (VEGF-C) expression in endothelial cells in vitro and to examine its underlying mechanisms. Methods: Human umbilical vein endothelial cells (HUVECs) were examined. VEGF-C mRNA expression in the cells was assessed using real-time PCR. VEGF-C protein and FGFR-I phosphorylation in the cells were measured with ELISA. RNA interference was used to downregulate the expression of matrix metalloproteinase-2 (MMP-2), fibroblast growth factor-1 (FGF-1) and FGF receptor-1 (FGFR-1). Results: Incubation of HUVECs with SIP (1, 5, and 10 mu mol/L) significantly increased VEGF-C expression. The effect was blocked by pretreatment with the MMP inhibitor GM6001 or the FGFR inhibitor SU5402, but not the EGFR inhibitor AGI478. The effect was also blocked in HUVECs that were transfected with FGFR-1 or MMP-2 siRNA. Furthermore, incubation of HUVECs with SIP (5 mu mol/L) significantly increased FGFR-I phosphorylation, which was blocked by GM6001. Moreover, knockdown of FGF-1, not FGF-2, in HUVECs with siRNAs, blocked SIP-induced VEGF-C expression. Conclusion: SIP induces VEGF-C expression through a MMP-2/ FGF-1/FGFR-1-dependent pathway in HUVECs.

引用

页码：360 / 366

页数：7

共 32 条

[1]

Expression pattern of fibroblast growth factors (FGFs), their receptors and antagonists in primary endothelial cells and vascular smooth muscle cells [J].