Wip1-dependent modulation of macrophage migration and phagocytosis

Yiting Tang, Bing Pan, Xin Zhou, Kai Xiong, Qian Gao, Lei Huang, Ying Xia, Ming Shen, Shulin Yang, Honglin Liu, Tao Tan, Jianjie Ma, Xuehong Xu, Yulian Mu*, Kui Li

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

16 Citationer (Scopus)
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Abstract

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.

OriginalsprogEngelsk
TidsskriftRedox Biology
Vol/bind13
Sider (fra-til)665-673
Antal sider9
ISSN2213-2317
DOI
StatusUdgivet - 2017

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