Lung endothelial cell-targeted peptide-guided bFGF promotes the regeneration after radiation induced lung injury

被引:36
作者
Guan, Dongwei [1 ]
Mi, Junwei [1 ]
Chen, Xi [1 ]
Wu, Yonghui [1 ]
Yao, Yuanjiang [1 ]
Wang, Linjie [1 ]
Xiao, Zhifeng [2 ]
Zhao, Yannan [2 ]
Chen, Bing [2 ]
Dai, Jianwu [1 ,2 ]
机构
[1] Third Mil Med Univ, Army Med Univ,State Key Lab Trauma Burns & Combin, Chongqing Engn Res Ctr Biomat & Regenerat Med,Ins, Chongqing Engn Res Ctr Nanomed,Coll Prevent Med, Chongqing 400038, Peoples R China
[2] Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing 100101, Peoples R China
基金
国家重点研发计划;
关键词
Basic fibroblast growth factor (bFGF); Lung endothelial cell; Radiation induced lung injury (RILI); Lung-targeted therapy; Vascular endothelial cell apoptosis; FIBROBLAST-GROWTH-FACTOR; NORMAL TISSUE-INJURY; INDUCED APOPTOSIS; PULMONARY-FIBROSIS; ANTIBODY FRAGMENT; PHAGE-DISPLAY; PROTECTION; INDUCTION; THERAPY; PATHWAY;
D O I
10.1016/j.biomaterials.2018.08.061
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Basic fibroblast growth factor (bFGF) can protect the lung against radiation-induced pulmonary vascular endothelial apoptosis and subsequent radiation-induced lung injury (RILI). However, guiding bFGF to pulmonary vascular endothelial cells is a key determinant for the success of bFGF therapy. To improve the lung-targeting ability of bFGF, a lung endothelial cell-targeting peptide was fused to bFGF (LET-bFGF). An in vitro biological activity assay indicated that fusion of LET did not affect the bioactivity of bFGF. In addition, the fused protein showed superior lung-targeting ability following intravenous injection. Upon injecting LET-bFGF intravenously after thorax radiation, LET-bFGF could better protect against pulmonary vascular endothelial cell apoptosis as early as 4 h post-radiation. Compared with native bFGF, enhanced therapeutic effects of LET-bFGF were also observed in terms of decreased vascular abnormalities, disorganized lung structure, inflammatory cell migration, and lung density at 2 months post-radiation. Therefore, lung endothelial cell-targeted bFGF may represent a promising remedy for RILI.
引用
收藏
页码:10 / 19
页数:10
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