A long noncoding RNA regulates inflammation resolution by mouse macrophages through fatty acid oxidation activation.

Abstract:

:Proper resolution of inflammation is vital for repair and restoration of homeostasis after tissue damage, and its dysregulation underlies various noncommunicable diseases, such as cardiovascular and metabolic diseases. Macrophages play diverse roles throughout initial inflammation, its resolution, and tissue repair. Differential metabolic reprogramming is reportedly required for induction and support of the various macrophage activation states. Here we show that a long noncoding RNA (lncRNA), lncFAO, contributes to inflammation resolution and tissue repair in mice by promoting fatty acid oxidation (FAO) in macrophages. lncFAO is induced late after lipopolysaccharide (LPS) stimulation of cultured macrophages and in Ly6Chi monocyte-derived macrophages in damaged tissue during the resolution and reparative phases. We found that lncFAO directly interacts with the HADHB subunit of mitochondrial trifunctional protein and activates FAO. lncFAO deletion impairs resolution of inflammation related to endotoxic shock and delays resolution of inflammation and tissue repair in a skin wound. These results demonstrate that by tuning mitochondrial metabolism, lncFAO acts as a node of immunometabolic control in macrophages during the resolution and repair phases of inflammation.

authors

Nakayama Y,Fujiu K,Yuki R,Oishi Y,Morioka MS,Isagawa T,Matsuda J,Oshima T,Matsubara T,Sugita J,Kudo F,Kaneda A,Endo Y,Nakayama T,Nagai R,Komuro I,Manabe I

doi

10.1073/pnas.2005924117

subject

Has Abstract

pub_date

2020-06-23 00:00:00

pages

14365-14375

issue

25

eissn

0027-8424

issn

1091-6490

pii

2005924117

journal_volume

117

pub_type

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