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Different PDGF Receptor Dimers Drive Distinct Migration Modes of the Mouse Skin Fibroblast

机译:不同的PDGF受体二聚体驱动小鼠皮肤成纤维细胞的不同迁移模式

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Background/Aims The migration of mesenchymal cells is a fundamental cellular process that has been implicated in many pathophysiological conditions and is induced by chemoattractants such as platelet-derived growth factors (PDGFs). However, the regulatory mechanisms shaping this migration remain to be elucidated. Methods Here, we prepared mouse skin fibroblasts inactivated for different PDGF receptor genes and systematically measured their chemotactic responses within a gradient of different chemoattractants. Results We found that PDGFRαβ and PDGFRββ dimers were strong inducers of random and directionally-persistent migration, respectively, that was sustained for up to 24 h. MAPK and PI3K were necessary to mediate random and directional migration, respectively. Directional migration was accompanied by abundant ventral stress fiber formation and consistent cell shape with less frequent formation of branch-like processes. Conclusion This is the first systematic study that characterized the chemotaxis mediated by three-different types of PDGFR dimers in mesenchymal cell migration. Our data demonstrate that PDGFR dimer formation is the critical step to determine the specific mode of fibroblast chemotaxis, while the accompanying cytoskeletal remodeling might contribute to migration persistence.
机译:背景/目的间充质细胞的迁移是一个基本的细胞过程,已牵涉到许多病理生理状况,并由趋化因子如血小板衍生的生长因子(PDGF)诱导。但是,影响这种迁移的监管机制仍有待阐明。方法在这里,我们制备了被不同PDGF受体基因灭活的小鼠皮肤成纤维细胞,并在不同趋化因子梯度内系统地测量了它们的趋化反应。结果我们发现PDGFRαβ和PDGFRββ二聚体分别是强随机诱导和定向持久迁移的诱导剂,其可持续长达24小时。 MAPK和PI3K分别是介导随机和方向迁移所必需的。定向迁移伴随着丰富的腹侧应力纤维形成和一致的细胞形状,而分支状过程的形成频率降低。结论这是第一个系统研究表征间质细胞迁移中由三种不同类型的PDGFR二聚体介导的趋化性。我们的数据表明,PDGFR二聚体的形成是确定成纤维细胞趋化性特定模式的关键步骤,而伴随的细胞骨架重塑可能会促进迁移持久性。

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