Akt2 is required for macrophage chemotaxis
Akt2 is required for macrophage chemotaxis
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Akt2 是巨噬细胞趋化性所必需的
DOI：
10.1002/eji.200838809
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发表时间：
2009-03-01
影响因子：
5.4
通讯作者：
Zhang, Ning
中科院分区：
文献类型：
--
作者：
Zhang, Baogang;Ma, Yongjie;Zhang, Ning
肿瘤相关巨噬细胞在肿瘤的发生和转移中起重要作用。巨噬细胞向肿瘤附近的运输由CSF-1（一种生长因子）介导。在这项研究中，我们研究了PKB/Akt在CSF-1诱导的巨噬细胞迁移中的作用。通过小干扰RNA破坏Akt 2表达损害了THP-1细胞和小鼠腹腔巨噬细胞的趋化性。趋化性信号通路的重要组成部分PKC zeta的磷酸化减少。LIMK/Cofilin，PKC zeta的下游，调节细胞迁移过程中的细胞骨架重排。Akt 2表达的破坏抑制CSF-1诱导的LIMK/Cofilin磷酸化，这导致肌动蛋白聚合和趋化性的缺陷。此外，MCP-1，一种趋化因子，诱导的巨噬细胞趋化性也受损。总之，我们的结果表明，Akt 2在CSF-1和趋化因子诱导的巨噬细胞趋化性中起着重要作用。
Tumor-associated macrophages play an important role in tumorigenesis and metastasis. Trafficking of macrophages to the proximity of tumors is mediated by CSF-1, a growth factor. In this study, we investigated the role of PKB/Akt in CSF-1-induced macrophage migration. Disruption of Akt2 expression by small interference RNA impaired chemotaxis of both THP-1 cells and mouse peritoneal macrophages. Phosphorylation of PKC zeta, an essential component in chemotaxis signaling pathway, was reduced. LIMK/Cofilin, downstream of PKC zeta, regulated cytoskeleton rearrangement during cell migration. Disruption of Akt2 expression inhibited CSF-1-induced LIMK/Cofilin phosphorylation, which contributed to defects in actin polymerization and chemotaxis. Furthermore, MCP-1, a chemokine, -induced macrophage chemotaxis was also impaired. Taken together, our results demonstrated that Akt2 plays an essential role in both CSF-1- and chemokine-induced chemotaxis of macrophages.