Vimentin蛋白调控五指山小型猪间充质干细胞迁移能力的分子机制

Wuzhishan mini-pig inbred is one of the unique resources in China, and is a comparatively ideal animal model for medical purpose.The migration of mesenchymal stem cells is closely related to tissue repair and organ reconstruction efficiency, and it has broad prospects for the application in tissue engineering and regenerative medicine. So far, the molecular mechanism for mesenchymal stem cells migration is not identified. Studies have shown that the mesenchymal stem cells in xenogeneic transplantation has no immune rejection phenomenon. In our previous studies, we found significant difference expression of Vimentin, a molecule involves in cell migration, between bone marrow mesenchymal stem cells and umbilical cord mesenchymal stem cells of Wuzhishan miniature pig by proteomic screening. However, the role of Vimentin in mini-pig's mesenchymal stem cells migration and the possible molecular mechanism are not fully discovered. In this study, with the use of mini-pig as a model, we will further explore the expression pattern, role and the regulatory mechanism of Vimentin on migration of mesenchymal stem cells. In addtion, we will investigate the relationship between Vimentin and the TGF-β1-Smad signal pathway，bulid the signal transduction network of Vimentin on regulating mesenchymal stem cells migration. It fully reflects interdisciplinary thinking and expands the scope of livestock germplasm resources, which can provide new ideas and theoretical basis in individual genome saving,transgenic pig preparing, artificial organs, tissue engineering, wound healing, basic and clinical research with the use of mesenchymal stem cells from mini-pig.

五指山小型猪近交群体是我国独特的小型猪资源，是比较理想的实验动物模型。间充质干细胞（MSCs）迁移能力与组织修复和器官重建效率密切相关，MSCs没有明显免疫原性，能够实现异种移植，在组织工程和再生医学中应用前景广阔。本组前期在五指山小型猪骨髓间充质干细胞和脐带间充质干细胞中筛选到与细胞迁移相关的重要差异蛋白Vimentin，但迄今其在MSCs迁移中的作用及调控机制研究仍未见报道。因此，本项目综合应用现代分子生物学和细胞生物学的研究手段，率先研究Vimentin蛋白调控小型猪MSCs迁移能力的分子机制，探讨其与TGF-β1-Smad等信号通路的相互关系，构建Vimentin影响MSCs迁移的信号传导网络。本项目拓展了家畜种质资源的应用范围，充分体现了学科交叉，为小型猪MSCs在个体基因组保存、转基因猪制备、人工器官、组织工程、创伤修复等基础和临床医学研究及应用提供新的思路和理论依据。

五指山小型猪近交群体是我国独特的小型猪资源，是比较理想的实验动物模型。间充质干细胞（mesenchmal stem cells，MSCs）迁移能力与组织修复和器官重建效率密切相关，MSCs没有明显免疫原性，能够实现异种移植，在组织工程和再生医学中前景广阔。本项目以五指山小型猪MSCs为实验材料，开展了Vimentin蛋白调控小型猪MSCs迁移能力的分子机制研究。结果表明Vimentin能够调控小型猪骨髓间充质干细胞（Bone marrow mesenchmal stem cells，BMMSCs）和脐带间充质干细胞（Umbilical cord derived MSCs，UCMSCs）的迁移能力，与WZSP MSCs的迁移存在正相关，与TGF-β1-Smad信号通路发生作用；筛选获得了多个与Vimentin蛋白互作的蛋白，功能验证发现其均可以正调控MSCs的迁移能力，并且表明部分蛋白是通过抑制RhoA-GTP的活性，增强p-AKT(ser473)的表达以及调节p-ERK1/2的水平来增强BMMSCs的迁移能力的。本研究不仅可以为基础研究提供安全可靠的MSCs，在组织工程材料的构建、评价体系中具有重要意义；而且可为组织损伤修复和临床治疗提供理论依据，在MSCs移植领域具有广阔的应用前景。本项目发表文章5篇，申报国家发明专利1项。