A C-terminal fragment BIGH3 protein with an RGDRGD motif inhibits corneal neovascularization in vitro and in vivo

文献类型： 外文期刊

第一作者： Ge, Hongyan

作者： Ge, Hongyan;Tian, Pei;Guan, Linan;Yin, Xiuli;Liu, Hanruo;Xiao, Nan;Luo, Xin;Sun, Yunduan;Qi, Donghua;Ni, Shuang;Liu, Ping;Xiong, Yongzhong

作者机构：

关键词： corneal neovascularization;anti-angiogenesis;BIGH3;RGDRGD

期刊名称：EXPERIMENTAL EYE RESEARCH （ 影响因子：3.467； 五年影响因子：3.811 ）

ISSN： 0014-4835

年卷期： 2013 年 112 卷

页码：

收录情况： SCI

摘要： An Arg-Gly-Asp (RGD) motif in the fourth FAS1 domain of the human BIGH3 (transforming growth factor-beta 1-inducible gene-h3) protein has been reported to play an important role in mediating tumor angiogenesis. The aim of this study was to investigate the inhibitory effect of a modified C-terminal fragment BIGH3 protein with an RGDRGD motif on corneal neovascularization in vitro and in vivo. Recombinant C-terminal fragment BIGH3 protein with wild-type sequence and modified C-terminal fragment BIGH3 protein containing an RGDRGD motif were successfully expressed and purified. We demonstrated that both proteins significantly inhibited vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cell (HUVEC) adhesion, migration, and tube formation and induced cell apoptosis but failed to inhibit HUVEC proliferation. We determined that the mechanism underlying this activity was an interaction between BIGH3 and alpha v beta 3 integrin, which blocked the phosphorylation of PI3K/Akt and ERK signaling pathways. The inhibitory effects of wild-type and modified C-terminal fragment BIGH3 proteins on angiogenesis were confirmed by a rabbit corneal neovascularization assay. More importantly, we provided evidence that the modified C-terminal fragment BIGH3 protein with an RGDRGD motif inhibited angiogenic activity far more effectively than did wild-type C-terminal fragment BIGH3. Collectively, our data show that a C-terminal fragment BIGH3 protein containing an RGDRGD motif might be promising as an effective drug in treating corneal neovascularization. (C) 2013 Elsevier Ltd. All rights reserved.

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[1]Modified BIGH3 with an RGDRGD motif promotes human corneal epithelial cell adhesion and migration In Vitro. Ge, Hongyan,Cao, Wenping,Leng, Fei,Chen, Weiye,Liu, Ping,Chen, Weiye. 2008

[2]CS5931, a Novel Polypeptide in Ciona savignyi, Represses Angiogenesis via Inhibiting Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases (MMPs). Liu, Ge,Wu, Ning,Liu, Ge,Liu, Ming,Wei, Jianteng,Huang, Haijuan,Zhang, Yuyan,Zhao, Jin,Xiao, Lin,Zheng, Lanhong,Lin, Xiukun. 2014

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