BMP-7经MEK/ERK通路上调CXCR4表达促进BM-MSCs向缺血再灌注肾脏归巢的作用研究

Bone marrow mesenchymal stem cells(BM-MSCs) has the properties of homing to the ischemic injuried tissue,but the homing proportion of BM-MSCs is very low.Therefore,to promote the BM-MSCs homing to the target organ is critical for BM-MSCs treating diseases. Stromal derived factor 1(SDF-1) and CXCR4 play an important role in promoting BM-MSCs homing to the injuried tissue.This project is based on previous research. We found that bone morphogenetic protein 7(BMP-7) modified BM-MSCs transplantation can increase the number of transplanted BM-MSCs migrating and colonizing to injuried kidney, and the expression of CXCR4 in BMP-7 modified BM-MSCs in vitro was enhanced.So, we hypothesized that BMP-7 up-regulating CXCR4 expression promotes BM-MSCs homing.This project plans to reveal the mechanism of BMP-7 promoting the expression of CXCR4 in BM-MSCs from MEK / ERK signaling pathway because of the importance of MEK/ERK signaling pathway in regulating the expression of CXCR4 and transfering the signal of BMP in cells.This study aims to reveal the mechanism of BMP-7 modified BM-MSCs transplantation for the treatment of renal ischemia reperfusion injury and provide a new idea to promote BM-MSCs homing.

骨髓间充质干细胞（BM-MSCs）具有向缺血损伤组织归巢的特性，但归巢比例较低，疗效受限。因此，促进BM-MSCs归巢至靶器官是BM-MSCs治疗疾病的关键。而基质衍生因子-1（SDF-1）和受体CXCR4形成SDF-1/ CXCR4轴在促进BM-MSCs向损伤组织归巢方面发挥重要作用。本项目基于前期研究中发现骨形态发生蛋白-7（BMP-7）修饰BM-MSCs移植能增加向损伤肾脏迁移并定植的BM-MSCs数量，并检测BMP-7修饰BM-MSCs表达CXCR4增强，故推测BMP-7上调CXCR4表达促进BM-MSCs归巢。鉴于MEK/ERK信号通路在调控CXCR4表达及介导BMP信号转导中的重要性，本项目拟从MEK/ERK通路入手研究BMP-7对CXCR4调控的机制。本研究进一步阐明BMP-7修饰BM-MSCs移植治疗肾脏缺血再灌注损伤的机制，为促进BM-MSCs归巢并提高疗效提供新的思路。

骨髓间充质干细胞（BM-MSCs）具有向缺血损伤组织归巢的特性，但归巢比例较低，疗效受限。因此，促进BM-MSCs归巢至靶器官是BM-MSCs治疗疾病的关键。而基质衍生因子-1（SDF-1）和受体CXCR4形成SDF-1/ CXCR4轴在促进BM-MSCs向损伤组织归巢方面发挥重要作用。本项目基于前期研究中发现骨形态发生蛋白-7（BMP-7）修饰BM-MSCs移植能增加向损伤肾脏迁移并定植的BM-MSCs数量，并检测BMP-7修饰BM-MSCs表达CXCR4增强，证实BMP-7通过MEK/ERK信号通路上调CXCR4表达促进BM-MSCs归巢，从而进一步阐明BMP-7修饰BM-MSCs移植治疗肾脏缺血再灌注损伤的机制，为促进BM-MSCs归巢并提高疗效提供了新的思路。