期刊
CELL METABOLISM
卷 33, 期 12, 页码 2398-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2021.10.004
关键词
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资金
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) : CRC829 [73111208]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) : CRC1218 [269925409]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) : Research Unit FOR2599 [3927 49992]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) : CRC1403 [414786233]
- Germany's Excel-lence Strategy - CECAD, EXC 2030 [390661388]
- Research Unit FOR2240 [EM48/5-2]
- Center for Molecular Med-icine
- DEBRA International Foundation
The study found that changes in cellular metabolism play a critical role in regulating macrophage functions during wound healing.
Wound healing is a coordinated process that initially relies on pro-inflammatory macrophages, followed by a pro-resolution function of these cells. Changes in cellular metabolism likely dictate these distinct activities, but the nature of these changes has been unclear. Here, we profiled early-versus late-stage skin wound macrophages in mice at both the transcriptional and functional levels. We found that glycolytic metabolism in the early phase is not sufficient to ensure productive repair. Instead, by combining conditional disruption of the electron transport chain with deletion of mitochondrial aspartyl-tRNA synthetase, followed by single-cell sequencing analysis, we found that a subpopulation of early-stage wound macrophages are marked by mitochondrial ROS (mtROS) production and HIF1a stabilization, which ultimately drives a pro-angiogenic program essential for timely healing. In contrast, late-phase, pro-resolving wound macrophages are marked by IL-4Ra-mediated mitochondrial respiration and mitohormesis. Collectively, we identify changes in mitochondrial metabolism as a critical control mechanism for macrophage effector functions during wound healing.
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