Serum amyloid A stimulates vascular endothelial growth factor receptor 2 expression and angiogenesis
Serum amyloid A stimulates vascular endothelial growth factor receptor 2 expression and angiogenesis
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血清淀粉样蛋白 A 刺激血管内皮生长因子受体 2 表达和血管生成。
DOI：
10.1007/s13105-015-0462-4
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发表时间：
2016-03-01
影响因子：
3.4
通讯作者：
An, Feng-shuang
中科院分区：
文献类型：
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作者：
Lv, Mei;Xia, Yan-fei;An, Feng-shuang
血清淀粉样蛋白A（SAA）是一种主要的急性期反应物，在许多疾病中调节血管生成。血管内皮生长因子受体2（VEGFR 2）是血管内皮生长因子（VEGF）的主要血管生成受体，但SAA和VEGFR 2之间相互作用的可能性尚未得到解决。在这里，我们研究了SAA是否刺激VEGFR 2的表达并促进体外血管生成。用重组SAA（rSAA）刺激人脐静脉内皮细胞（HUVECs），Western blot和实时荧光定量PCR检测VEGF 2 mRNA和蛋白表达。用甲酰肽受体样1（FPRL 1）激动剂（WKYMVm）、拮抗剂（WRW 4）和丝裂原活化蛋白激酶（MAPK）抑制剂研究VEGFR 2的调节机制。我们发现SAA以时间和剂量依赖性的方式诱导HUVECs中VEGFR 2的表达。此外，SAA促进HUVEC中的管形成。SAA对管形成的影响是VEGFR 2表达增加的结果，其被多血管激酶受体抑制剂BIBF 1120阻断。SAA的这些活性似乎是由FPRL 1/MAPK信号通路介导的，因为它们被WKYMVm模拟并被WRW 4和MAPK抑制剂废除。这些观察结果表明SAA通过FPRL 1/MAPK信号通路诱导VEGFR 2表达并促进HUVEC中的管形成，从而为控制血管生成提供了潜在的靶点。
Serum amyloid A (SAA), a major acute-phase reactant, modulates angiogenesis in many diseases. Vascular endothelial growth factor receptor 2 (VEGFR2) is the primary angiogenic receptor for vascular endothelial growth factor (VEGF), but the possibility of an interaction between SAA and VEGFR2 has not yet been resolved. Here, we investigated if SAA stimulates the expression of VEGFR2 and promotes angiogenesis in vitro. Human umbilical vein endothelial cells (HUVECs) were stimulated with recombinant SAA (rSAA), and the messenger RNA (mRNA) and protein expression of VEGFR2 was detected by Western blot analysis and quantitative real-time PCR. Formyl peptide receptor-like 1 (FPRL1) agonist (WKYMVm) and antagonist (WRW4) and inhibitors of mitogen-activated protein kinases (MAPKs) were used to investigate the mechanism of regulation of VEGFR2. We show that SAA induces VEGFR2 expression in a time-and dose-dependent manner in HUVECs. In addition, SAA promotes tube formation in HUVECs. The effect of SAA on tube formation was shown to be the result of an increase in VEGFR2 expression, which was blocked by the multi-angiokinase receptor inhibitor BIBF1120. These activities of SAA appear to be mediated by FPRL1/MAPK signaling pathways, as they were mimicked by WKYMVm and abrogated by WRW4 and inhibitors of MAPKs. These observations indicate that SAA induces VEGFR2 expression and promotes tube formation in HUVECs via the FPRL1/MAPK signaling pathway, thus providing a potential target for the control of angiogenesis.