CXCL12／CXCR7通路诱导祖细胞迁移和血管新生协同促进脊髓损伤修复

本课题以申请人近年来在神经祖细胞生存和迁移的研究进展为基础，探讨重要趋化因子CXCL12诱导神经祖细胞迁移和血管新生，进而促进神经修复的过程和机制。研究将揭示CXCL12/CXCR7/Arrestin-2/Rac1通路对内皮细胞／神经祖细胞的协同诱导作用，以及潜在调控神经血管单元的功能重建作用。本课题也将提示在微环境炎症状态下CXCR7高表达的病理生理意义和优势作用。研究也将对CXCR7敲除动物的细胞行为进行分析，从而进一步地阐明CXCR7促进神经和血管再生的独立作用。课题最终将明确CXCL12或CXCR7激动剂TC14012对神经修复和功能康复的正性作用，为神经康复的神经调节治疗提供新的策略提供依据。

Abstract: Based on the foundation on the our study of cell polarization, migration and differentiation of endogenous neural stem cells in central nerve system, the project will work on the mechanism of cell activation/differentiation, restoration of neurovascular units and neural repair with stimulation of CXCL12 or TC14012, an specific agonist of receptor CXCR7. The study will reveal that CXCL12/CXCR7/Arrestin-2/Rac1 pathway directly induces cell migration, tube formation and neurovascular restoration in neural inflammative environment during acute spinal cord injury with the higher expression of CXCR7. The hypothesis is also confirmed by using CXCR7 knockout mice. The project will strongly suggest that CXCL12/TC14012 are both activators of neurovascular units and enhance neural regeneration and clinical neural rehabilitation. The TC14012 may be a potential candidate of drug development.