TWEAK is an endothelial cell growth and chemotactic factor that also potentiates FGF-2 and VEGF-A mitogenic activity
TWEAK is an endothelial cell growth and chemotactic factor that also potentiates FGF-2 and VEGF-A mitogenic activity
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DOI：
10.1161/01.atv.0000062883.93715.37
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发表时间：
2003-04-01
影响因子：
8.7
通讯作者：
Winkles, JA
中科院分区：
文献类型：
--
作者：
Donohue, PJ;Richards, CM;Winkles, JA
TWEAK是肿瘤坏死因子超家族的成员，与Fn 14受体结合并刺激体内血管生成。在这项研究中，我们研究了Fn 14基因在人内皮细胞（ECs）的表达，并研究了TWEAK，单独或与成纤维细胞生长因子-2（FGF-2）或血管内皮生长因子-A（VEGF-A）的组合，对EC增殖，迁移和存活的影响。我们还确定了可溶性Fn 14-Fc融合蛋白是否可以抑制ECs上的TWEAK生物活性，并研究了ECs.Methods和结果中的TWEAK信号转导，我们发现FGF-2和VEGF-A都可以诱导ECs中Fn 14 mRNA的表达。TWEAK是内皮细胞的促分裂原，其增殖活性可被Fn 14-Fc诱饵受体抑制。此外，TWEAK处理激活了EC中的几种细胞内信号传导途径，并增强了FGF-2和VEGF-A刺激的EC增殖。TWEAK也有EC趋化活性，但它没有促进EC survival. Conclusions这些结果表明，TWEAK是EC的生长和迁移因子，但不是生存因子。TWEAK还可以增强FGF-2和VEGF-A对EC的促有丝分裂活性。因此，TWEAK可以单独以及与FGF-2或VEGF-A组合起作用以调节病理性血管生成。
Objective-TWEAK, a member of the tumor necrosis factor superfamily, binds to the Fn14 receptor and stimulates angiogenesis in vivo. In this study, we investigated Fn14 gene expression in human endothelial cells (ECs) and examined the effect of TWEAK, added either alone or in combination with fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor-A (VEGF-A), on EC proliferation, migration, and survival in vitro. We also determined whether a soluble Fn14-Fc fusion protein could inhibit TWEAK biologic activity on ECs and investigated TWEAK signal transduction in ECs.Methods and Results-We found that both FGF-2 and VEGF-A could induce Fn14 mRNA expression in ECs. TWEAK was a mitogen for ECs, and this proliferative activity could be inhibited by an Fn14-Fc decoy receptor. Furthermore, TWEAK treatment activated several intracellular signaling pathways in ECs and potentiated FGF-2- and VEGF-A stimulated EC proliferation. TWEAK also had EC chemotactic activity, but it did not promote EC survival.Conclusions-These results indicate that TWEAK is an EC growth and migration factor but not a survival factor. TWEAK can also enhance both FGF-2 and VEGF-A mitogenic activity on ECs. Thus, TWEAK may act alone as well as in combination with FGF-2 or VEGF-A to regulate pathological angiogenesis.