A C-terminal fragment BIGH3 protein with an RGDRGD motif inhibits corneal neovascularization in?vitro and in?vivo
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- 作者：Hongyan Ge ; Pei Tian ; Linan Guan ; Xiuli Yin ; Hanruo Liu ; Nan Xiao ; Yongzhong Xiong ; Xin Luo ; Yunduan Sun ; Donghua Qi ; Shuang Ni ; Ping Liu
- 关键词：corneal neovascularization ; anti-angiogenesis ; BIGH3 ; RGDRGD
- 刊名：Experimental Eye Research
- 出版年：2013
- 出版时间：July, 2013
- 年：2013
- 卷：112
- 期：Complete
- 页码：10-20
- 全文大小：1681 K
文摘
An Arg-Gly-Asp (RGD) motif in the fourth FAS1 domain of the human BIGH3 (transforming growth factor-¦Â1-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 ¦Áv¦Â3 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.