β-Catenin-regulated myeloid cell adhesion and migration determine wound healing
β-Catenin-regulated myeloid cell adhesion and migration determine wound healing
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DOI：
10.1172/jci62059
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发表时间：
2014-06-01
影响因子：
15.9
通讯作者：
Alman, Benjamin A.
中科院分区：
文献类型：
--
作者：
Amini-Nik, Saeid;Cambridge, Elizabeth;Alman, Benjamin A.
β-连环蛋白/T 细胞因子依赖性转录程序在皮肤伤口修复过程中对于调节疤痕大小至关重要；然而，在愈合过程中，肉芽组织中特定细胞类型中β-连环蛋白活性和功能的相对贡献尚不清楚。在这里，细胞谱系追踪揭示了β-连环蛋白具有转录活性的细胞表达了骨髓谱系特征的基因谱。含有巨噬细胞特异性删除β-连环蛋白基因的小鼠表现出皮肤伤口愈合不足，这是由于巨噬细胞特异性的迁移缺陷、与成纤维细胞的粘附以及产生TGF-β 1的能力所致。在受辐射的小鼠中，只有表达β-连环蛋白的巨噬细胞能够挽救伤口愈合缺陷。对从肥厚性疤痕和正常疤痕患者收集的疤痕组织进行评估揭示了伤口内巨噬细胞数量、β-连环蛋白水平和细胞结构之间的相关性。我们的数据表明，β-连环蛋白调节骨髓细胞运动和粘附，并且β-连环蛋白介导的巨噬细胞运动有助于间充质细胞的数量和皮肤损伤后最终疤痕的大小。
A beta-catenin/T cell factor-dependent transcriptional program is critical during cutaneous wound repair for the regulation of scar size; however, the relative contribution of beta-catenin activity and function in specific cell types in the granulation tissue during the healing process is unknown. Here, cell lineage tracing revealed that cells in which beta-catenin is transcriptionally active express a gene profile that is characteristic of the myeloid lineage. Mice harboring a macrophage-specific deletion of the gene encoding beta-catenin exhibited insufficient skin wound healing due to macrophage-specific defects in migration, adhesion to fibroblasts, and ability to produce TGF-beta 1. In irradiated mice, only macrophages expressing beta-catenin were able to rescue wound-healing deficiency. Evaluation of scar tissue collected from patients with hypertrophic and normal scars revealed a correlation between the number of macrophages within the wound, beta-catenin levels, and cellularity. Our data indicate that beta-catenin regulates myeloid cell motility and adhesion and that beta-catenin-mediated macrophage motility contributes to the number of mesenchymal cells and ultimate scar size following cutaneous injury.