SDF-1/CXCR4与α4-整合素参与血管内皮祖细胞的动员和募集的最新研究进展  

The latest research progress of SDF-1/CXCR4 andα4-integrin involved in the mobilization and recruitment of vascular endothelial progenitor cells

作　　者：吕洋 周扬 李红[1] Lyu Yang;Zhou Yang;Li Hong(Department of Ophthalmology,the 940th Hospital of Joint Logistics Support Force of Chinese PLA,Lanzhou 730000,China;The First Clinical Medicine College of Gansu University of Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]中国人民解放军联勤保障部队第九四○医院眼科中心,兰州730000 [2]甘肃省中医药大学第一临床医学院,兰州730000

出　　处：《国际免疫学杂志》2022年第6期616-621,共6页International Journal of Immunology

基　　金：国家自然科学基金资助项目(82000926,81500748);联勤保障部队第九四○医院院基金(2021yxky033,2021yxky057);2022年中央高校基本科研业务费专项资金资助(31920220105,31920220109)。

摘　　要：血管内皮祖细胞的动员和募集在很大程度上受基质细胞衍生因子-1(stromal cell-derived factors-1,SDF-1)、CXC趋化因子受体4(CXC chemokine receptor 4,CXCR4)和α4-整合素(α4-integrin)信号通路的调控,这两种信号通路均依赖c-kit活性,并对于血管内皮祖细胞在缺血区域的驻留起到非常关键的作用。目前,大多数临床试验是通过注射粒细胞集落刺激因子(granulocyte colony stimulating factor,G-CSF)动员细胞,而G-CSF同时激活了细胞外蛋白酶,破坏细胞外表面粘附分子(α4-整合素及CXCR4等),抑制了血管内皮祖细胞在缺血组织的驻留,靶向血管内皮祖细胞治疗尚不能达到前期研究中的疗效。AMD3100通过阻断SDF-1/CXCR4的结合,与G-CSF联用能够改善机体的应答能力。在缺血区域提高SDF-1的表达水平可提高血管内皮祖细胞募集的能力,从而改善干细胞治疗效果。The mobilization and recruitment of vascular endothelial progenitor cells are largely regulated by stromal cell-derived factor-1(SDF-1),CXC chemokine receptor 4(CXCR4)signaling pathways andα4-integrin signaling pathways.Both of these signaling pathways depend on c-kit activity.The SDF-1/CXCR4 andα4-integrin signaling pathways play a critical role in the retention of vascular endothelial progenitor cells in the ischemic area.At present,most clinical trials are carried on via mobilizing cells by injecting granulocyte colony stimulating factor(G-CSF),however,G-CSF could also activate extracellular proteases and remove adhesion molecules on the surface of cells.For example:α4-integrin and CXCR4.Therefore,in the ischemic area,the number of cells mobilized by G-CSF may decrease.Targeted vascular endothelial progenitor cell therapy has not yet been able to achieve the efficacy seen in previous studies.AMD3100 is able to improve the body's response capacity by blocking SDF1/CXCR4 binding in combination with GCSF.In the ischemic regions,increasing the expression level of SDF1 could improve the ability of vascular endothelial progenitor cells recruitment,thus improving the effect of stem cell therapy.

关 键 词：SDF-1/CXCR4 α4-整合素 血管内皮祖细胞 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]