Migratory macrophages play critical roles in tissue development, homeostasis and disease, so it is important to understand how their migration machinery is regulated. Whole-transcriptome sequencing revealed that CSF-1-stimulated differentiation of bone marrow-derived precursors into mature macrophages is accompanied by widespread, profound changes in the expression of genes regulating adhesion, actin cytoskeletal remodeling and extracellular matrix degradation. Significantly altered expression of almost 40% of adhesion genes, 60-86% of Rho family GTPases, their regulators and effectors and over 70% of extracellular proteases occurred. The gene expression changes were mirrored by changes in macrophage adhesion associated with increases in motility and matrix-degrading capacity. IL-4 further increased motility and matrix-degrading capacity in mature macrophages, with additional changes in migration machinery gene expression. Finally, siRNA-induced reductions in the expression of the core adhesion proteins paxillin and leupaxin decreased macrophage spreading and the number of adhesions, with distinct effects on adhesion and their distribution, and on matrix degradation. Together, the datasets provide an important resource to increase our understanding of the regulation of migration in macrophages and to develop therapies targeting disease-enhancing macrophages.

中文翻译：

---

CSF-1 诱导的小鼠巨噬细胞分化中粘附、运动和基质降解基因表达的变化。

迁移性巨噬细胞在组织发育、体内平衡和疾病中发挥着关键作用，因此了解它们的迁移机制是如何调节的非常重要。全转录组测序表明，CSF-1刺激骨髓源性前体细胞分化为成熟巨噬细胞，同时伴随着调节粘附、肌动蛋白细胞骨架重塑和细胞外基质降解的基因表达的广泛而深刻的变化。近 40% 的粘附基因、60-86% 的 Rho 家族 GTPases、它们的调节子和效应子以及超过 70% 的细胞外蛋白酶的表达发生了显着改变。基因表达的变化反映在与运动性和基质降解能力增加相关的巨噬细胞粘附的变化上。IL-4 进一步增加了成熟巨噬细胞的运动性和基质降解能力，并导致迁移机制基因表达发生额外变化。最后，siRNA诱导的核心粘附蛋白桩蛋白和亮氨酸蛋白表达的减少减少了巨噬细胞的扩散和粘附的数量，对粘附及其分布以及基质降解具有明显的影响。总之，这些数据集提供了重要的资源，可以增加我们对巨噬细胞迁移调节的理解，并开发针对增强疾病的巨噬细胞的疗法。