Wip1-dependent modulation of macrophage migration and phagocytosis
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- 1-s2.0-S2213231717304159-main
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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.
Originalsprog | Engelsk |
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Tidsskrift | Redox Biology |
Vol/bind | 13 |
Sider (fra-til) | 665-673 |
Antal sider | 9 |
ISSN | 2213-2317 |
DOI | |
Status | Udgivet - 2017 |
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