Jung Mi Yeon, Thapa Narendra, Kim Jung Eun, Yang Jung Duk, Cho Byung Chae, Kim In San
Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Korea.
Exp Mol Med. 2007 Oct 31;39(5):663-72. doi: 10.1038/emm.2007.72.
An extracellular matrix protein plays an important role in skin wound healing. In the present study, we engineered a recombinant protein encompassing the 9(th) and 10(th) type III domains of fibronectin, and 4(th) FAS1 domain of betaig-h3. This recombinant protein, in total, harbors four known-cell adhesion motifs for integrins: Pro-His-Ser-Arg-Asn (PHSRN) and Arg-Gly-Asp (RGD) in 9(th) and 10(th) type III domains of fibronectin, respectively, and Glu-Pro-Asp-Ile-Met (EPDIM) and Try-His (YH) in 4(th) FAS1 domain of betaig-h3, were designated to tetra-cell adhesion motifs (T-CAM). In vitro studies showed T-CAM supporting adhesion, migration and proliferation of different cell types including keratinocytes and fibroblasts. In an animal model of full-thickness skin wound, T-CAM exhibited excellent wound healing effects, superior to both 4(th) FAS1 domain of betaig-h3 or 9(th) and 10(th) type III domains of fibronectin. Based on these results, T-CAM can be applied where enhancement of cell adhesion, migration and proliferation are desired, and it could be developed into novel wound healing drug.
一种细胞外基质蛋白在皮肤伤口愈合中起着重要作用。在本研究中,我们构建了一种重组蛋白,其包含纤连蛋白的第9和第10个III型结构域以及βig-h3的第4个FAS1结构域。这种重组蛋白总共含有四个已知的整合素细胞黏附基序:纤连蛋白第9和第10个III型结构域中的脯氨酸-组氨酸-丝氨酸-精氨酸-天冬酰胺(PHSRN)和精氨酸-甘氨酸-天冬氨酸(RGD),以及βig-h3第4个FAS1结构域中的谷氨酸-脯氨酸-天冬氨酸-异亮氨酸-甲硫氨酸(EPDIM)和酪氨酸-组氨酸(YH),被命名为四细胞黏附基序(T-CAM)。体外研究表明,T-CAM能支持包括角质形成细胞和成纤维细胞在内的不同细胞类型的黏附迁移和增殖。在全层皮肤伤口的动物模型中,T-CAM表现出优异的伤口愈合效果,优于βig-h3的第4个FAS1结构域或纤连蛋白的第9和第10个III型结构域。基于这些结果,T-CAM可应用于需要增强细胞黏附、迁移和增殖的地方,并有望开发成为新型伤口愈合药物。