Abstract

Understanding the mechanisms of glial scar formation by reactive astrocytes is crucial for elaborating a therapeutic strategy to brain and spinal cord injury. However, the extrinsic mechanisms that drive the polarization of reactive astrocytes, the first step in glial scar formation, remain poorly understood. Here, using an in vitro chemotaxis assay as an experimental model for polarization, we observed that Il4-M2 macrophages are stronger inducers of reactive astrocytes’ polarization, compared to naive or M1 macrophages. Then, we showed that both β1-integrin and Wnt/β-catenin pathways in astrocytes are required for this polarization in vitro and in vivo after spinal cord crush injury in mice. These findings provide molecular targets for manipulating the polarization of reactive astrocytes in order to potentially enhance the healing of SCI lesions.

中文翻译：

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M2巨噬细胞介导的Wnt /β-Catenin途径活化增强了反应性星形胶质细胞对脊髓损伤的应答极化

摘要

了解反应性星形胶质细胞形成胶质瘢痕的机制对于拟定脑和脊髓损伤的治疗策略至关重要。然而，外源性机制驱动反应性星形胶质细胞的极化，胶质疤痕形成的第一步，仍然知之甚少。在这里，使用体外趋化性测定作为极化的实验模型，我们观察到与天然或M1巨噬细胞相比，Il4-M2巨噬细胞是更强的反应性星形胶质细胞极化诱导剂。然后，我们表明星形胶质细胞中的β1-整合素和Wnt /β-catenin通路在小鼠脊髓压迫性损伤后的体内和体外均需要这种极化作用。这些发现为操纵反应性星形胶质细胞的极化提供了分子靶标，以潜在地增强SCI病变的愈合。