Understanding the circuits that promote an efficient resolution of inflammation is crucial to deciphering the molecular and cellular processes required to promote tissue repair. Macrophages play a central role in the regulation of inflammation, resolution, and repair/regeneration. Using a model of skeletal muscle injury and repair, herein we identified annexin A1 (AnxA1) as the extracellular trigger of macrophage skewing toward a pro-reparative phenotype. Brought into the injured tissue initially by migrated neutrophils, and then overexpressed in infiltrating macrophages, AnxA1 activated FPR2/ALX receptors and the downstream AMPK signaling cascade, leading to macrophage skewing, dampening of inflammation, and regeneration of muscle fibers. Mice lacking AnxA1 in all cells or only in myeloid cells displayed a defect in this reparative process. In vitro experiments recapitulated these properties, with AMPK-null macrophages lacking AnxA1-mediated polarization. Collectively, these data identified the AnxA1/FPR2/AMPK axis as an important pathway in skeletal muscle injury regeneration.

中文翻译：

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膜联蛋白A1驱动巨噬细胞偏斜，以通过AMPK激活来加速肌肉再生。

了解促进炎症有效解决的途径对于破译促进组织修复所需的分子和细胞过程至关重要。巨噬细胞在炎症，消融和修复/再生的调节中起着核心作用。使用骨骼肌损伤和修复模型，我们在这里确定膜联蛋白A1（AnxA1）是巨噬细胞偏向亲表型的细胞外触发。最初通过迁移的中性粒细胞进入受伤的组织，然后在浸润的巨噬细胞中过表达，AnxA1激活FPR2 / ALX受体和下游的AMPK信号级联，导致巨噬细胞歪斜，消炎和肌肉纤维再生。在所有细胞中或仅在骨髓细胞中缺乏AnxA1的小鼠在该修复过程中显示出缺陷。体外实验概括了这些特性，而缺少AnxA1介导的极化的AMPK空巨噬细胞。总体而言，这些数据确定了AnxA1 / FPR2 / AMPK轴是骨骼肌损伤再生的重要途径。