Human VE-Cadherin Fusion Protein as an Artificial Extracellular Matrix Enhancing the Proliferation and Differentiation Functions of Endothelial Cell
Human VE-Cadherin Fusion Protein as an Artificial Extracellular Matrix Enhancing the Proliferation and Differentiation Functions of Endothelial Cell
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人VE-钙粘蛋白融合蛋白作为人工细胞外基质增强内皮细胞的增殖和分化功能
DOI：
10.1021/acs.biomac.5b01467
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发表时间：
2016-03-01
影响因子：
6.2
通讯作者：
Yang, Jun
中科院分区：
文献类型：
--
作者：
Xu, Ke;Shuai, Qizhi;Yang, Jun
为了增强内皮细胞捕获和促进工程组织的血管化，我们生物合成并表征了由人血管内皮-钙粘蛋白细胞外结构域和免疫球蛋白IgG Fc区（ve -cad-Fc）组成的重组融合蛋白，作为生物人工细胞外基质。hVE-cad-Fc蛋白自然形成同型二聚体，并通过稳定吸附在聚苯乙烯板上构建了hVE-cad-Fc基质。原子力显微镜分析显示ve -cad- fc分布均匀，呈纳米棒形貌。hVE-cad-Fc基质显著促进人脐静脉内皮细胞（HUVECs）的粘附和增殖，呈成纤维样细胞形态。此外，ve -cad- fc基质改善了与血管化密切相关的HUVECs迁移、vWF表达和NO释放。此外，ve -cad- fc基质激活内源性VE-cadherin/ β -catenin蛋白，并有效触发细胞内信号，如F-actin应激纤维、p-FAK、AKT和Bcl-2。综上所述，hVE-cad-Fc可能是一种很有前途的生物人工基质，可以促进组织工程中的血管化。
In an attempt to enhance endothelial cell capture and, promote the vascularization of engineered tissue, we biosynthesized and characterized the recombinant fusion protein consisting of human vascular endothelial-cadherin extracellular domain and immunoglobulin IgG Fc region (hVE-cad-Fc) to serve as a bioartificial extracellular matrix. The hVE-cad-Fc protein naturally formed homodimers and was used to construct hVE-cad-Fc matrix by stably adsorbing on polystyrene plates. Atomic force microscop assay showed uniform hVE-cad-Fc distribution with nanorod topography. The hVE-cad-Fc matrix markedly promoted human umbilical vein endothelial cells (HUVECs) adhesion and proliferation with fibroblastoid morphology. Additionally, the hVE-cad-Fc matrix improved HUVECs migration, vWF expression, and NO release, which are closely related to vascularization. Furthermore, the hVE-cad-Fc matrix activated endogenous VE-cadherin/beta-catenin proteins and effectively triggered the intracellular signals such as F-actin stress fiber, p-FAK, AKT, and Bcl-2. Taken together, hVE-cad-Fc could be a promising bioartificial matrix to promote vascularization in tissue engineering.