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.lncFAOis induced late after lipopolysaccharide (LPS) stimulation of cultured macrophages and in Ly6Chimonocyte-derived macrophages in damaged tissue during the resolution and reparative phases. We found thatlncFAOdirectly interacts with the HADHB subunit of mitochondrial trifunctional protein and activates FAO.lncFAOdeletion 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,lncFAOacts as a node of immunometabolic control in macrophages during the resolution and repair phases of inflammation.
Funder
Ministry of Education, Culture, Sports, Science and Technology
Japan Agency for Medical Research and Development
MEXT | JST | Precursory Research for Embryonic Science and Technology
MSD Life Science Foundation
Japan Foundation for Applied Enzymology
Takeda Science Foundation
Uehara Memorial Foundation
Publisher
Proceedings of the National Academy of Sciences
Cited by
42 articles.
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