Tang Yiting, Pan Bing, Zhou Xin, Xiong Kai, Gao Qian, Huang Lei, Xia Ying, Shen Ming, Yang Shulin, Liu Honglin, Tan Tao, Ma Jianjie, Xu Xuehong, Mu Yulian, Li Kui
State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
Redox Biol. 2017 Oct;13:665-673. doi: 10.1016/j.redox.2017.08.006. Epub 2017 Aug 12.
Macrophage accumulation within the vascular wall is a hallmark of atherosclerosis. Controlling macrophage conversion into foam cells remains a major challenge for treatment of atherosclerotic diseases. Here, we show that Wip1, a member of the PP2C family of Ser/Thr protein phosphatases, modulates macrophage migration and phagocytosis associated with atherosclerotic plaque formation. Wip1 deficiency increases migratory and phagocytic activities of the macrophage under stress conditions. Enhanced migration of Wip1 macrophages is mediated by Rac1-GTPase and PI3K/AKT signalling pathways. Elevated phagocytic ability of Wip1 macrophages is linked to CD36 plasma membrane recruitment that is regulated by AMPK activity. Our study identifies Wip1 as an intrinsic negative regulator of macrophage chemotaxis. We propose that Wip1-dependent control of macrophage function may provide avenues for preventing or eliminating plaque formation in atherosclerosis.
巨噬细胞在血管壁内的积聚是动脉粥样硬化的一个标志。控制巨噬细胞转化为泡沫细胞仍然是治疗动脉粥样硬化疾病的一项重大挑战。在此，我们表明Wip1（丝氨酸/苏氨酸蛋白磷酸酶PP2C家族的一员）可调节与动脉粥样硬化斑块形成相关的巨噬细胞迁移和吞噬作用。Wip1缺陷会增加应激条件下巨噬细胞的迁移和吞噬活性。Wip1缺陷型巨噬细胞迁移增强是由Rac1 - GTP酶和PI3K/AKT信号通路介导的。Wip1缺陷型巨噬细胞吞噬能力的提高与受AMPK活性调节的CD36质膜募集有关。我们的研究确定Wip1是巨噬细胞趋化性的一种内在负调节因子。我们提出，Wip1依赖性地控制巨噬细胞功能可能为预防或消除动脉粥样硬化中的斑块形成提供途径。
