Different PDGF Receptor Dimers Drive Distinct Migration Modes of the Mouse Skin Fibroblast
Different PDGF Receptor Dimers Drive Distinct Migration Modes of the Mouse Skin Fibroblast
复制标题
不同的 PDGF 受体二聚体驱动小鼠皮肤成纤维细胞不同的迁移模式
DOI：
10.1159/000495594
复制
发表时间：
2018
影响因子：
--
通讯作者：
Sasahara Masakiyo
中科院分区：
文献类型：
--
作者：
Yamada Kohta;Hamashima Takeru;Ishii Yoko;Yamamoto Seiji;Okuno Noriko;Yoshida Naofumi;Yamada Moe;Huang Ting Ting;Shioda Norifumi;Tomihara Kei;Fujimori Toshihiko;Mori Hisashi;Fukunaga Kohji;Noguchi Makoto;Sasahara Masakiyo
间充质细胞的迁移是一个基本的细胞过程，与许多病理生理条件有关，并由血小板衍生生长因子（PDGFs）等趋化因子诱导。然而，形成这种迁移的监管机制仍有待阐明。MethodsHere，我们准备了小鼠皮肤成纤维细胞灭活不同的PDGF受体基因，并系统地测量其趋化反应的梯度内的不同chemoattractants.ResultsWe发现，PDGFRαβ和PDGFRββ二聚体是强诱导剂的随机和定向持久的迁移，分别是持续长达24小时。MAPK和PI3K分别是介导随机和定向迁移所必需的。定向迁移是伴随着丰富的腹侧应力纤维的形成和一致的细胞形状与较少的分支状processes.ConclusionThis的频繁形成是第一个系统的研究，其特点是由三种不同类型的PDGFR二聚体介导的趋化性间充质细胞迁移。我们的数据表明，PDGFR二聚体的形成是决定成纤维细胞趋化性的特定模式的关键步骤，而伴随的细胞骨架重塑可能有助于迁移的持久性。
Background/AimsThe 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.MethodsHere, we prepared mouse skin fibroblasts inactivated for different PDGF receptor genes and systematically measured their chemotactic responses within a gradient of different chemoattractants.ResultsWe 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.ConclusionThis 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.