JAM-A基因修饰的间充质干细胞通过Tiam1/Rac1信号通路促进肝损伤修复的研究

Mesenchymal stem cell (MSC) transplantation is one of the potential tools for the treatment of endogenous liver injury, but the poor targeted migration ability after transplantation limit its application. Promoting the targeted migration of MSC may be an effective method to improve the efficiency of MSC transplantation. JAM-A has been shown to promote the migration and proliferation of epithelial cells, and the effects of JAM-A are associated with binding of intracellular PDZ binding sequences. Taim1 contains PDZ binding sequence, and Taim1/Rac1 signaling pathway is involved in cell migration. The role of JAM-A and Taim1/Rac1 signaling pathway in repairing liver injury in MSC is rarely reported. In our previous study, it was found that the up-regulation of JAM-A in MSC could promote the migration of MSC to the injured liver. Based on the above theories and results, the aim of this project is to study the promoting effect of JAM-A on repairing liver injury by transplanting MSC with different JAM-A expression levels. The relationship between Tiam1/Rac1 signaling pathway with the mechanism of JAM-A in promoting MSC repairing hepatic injury will be verified by in vitro experiments, which will lay a theoretical foundation for improving the targeting migration ability of MSC and repairing liver injury.

间充质干细胞（MSC）移植是用于治疗内源性肝损伤的潜在手段之一，但移植后靶向迁移能力弱成为限制其应用的瓶颈，促进MSC的靶向迁移可能成为提高MSC移植效率的有效手段。连接黏附分子JAM-A已被证实可促进上皮细胞的迁移与增殖，JAM-A发挥作用与其结合细胞内PDZ结合序列相关。Taim1分子含有PDZ结合序列，且Taim1/Rac1信号通路参与细胞迁移，然而关于JAM-A和Taim1/Rac在MSC修复肝损伤中的作用及其机制鲜有报道。前期预实验发现，上调MSC中JAM-A的表达水平可促进MSC向损伤肝脏的迁移。基于此，本项目拟通过移植不同JAM-A表达水平的MSC，研究JAM-A修饰对MSC在肝损伤修复中的促进作用，验证JAM-A促进MSC修复肝损伤的作用机制与Tiam1/Rac1信号通路的关系，为提高MSC的靶向迁移能力以及肝损伤修复奠定理论基础。

间充质干细胞是用于治疗内源性肝损伤的潜在手段之一，但移植后靶向迁移能力弱成为限制其应用的瓶颈，促进MSC的靶向迁移可能成为提高MSC移植效率的有效手段。连接黏附分子JAM-A已被证实可促进上皮细胞的迁移与增殖，然而关于JAM-A在MSC修复肝损伤中的作用及其机制鲜有报道。本项目通过构建过表达JAM-A的间充质干细胞，建立特异性肝损伤模型，移植JAM-A不同表达水平的MSC，发现JAM-A表达上调可促进MSC对肝损伤的保护作用，通过体外实验揭示了JAM-A促进MSC修复肝损伤的作用机制，为提高MSC的靶向迁移能力以及肝损伤修复奠定理论基础。