线粒体代谢协调伤口愈合期间巨噬细胞的阶段性修复过程

http://paper.sciencenet.cn/htmlpaper/2021/10/202110312037281867465.shtm

作者：小柯机器人 发布时间：2021/10/31 20:37:28

本期文章：《细胞—代谢》：Online/在线发表

德国科隆大学Sabine A. Eming研究团队发现，线粒体代谢协调伤口愈合期间巨噬细胞的阶段性修复过程。相关论文于2021年10月28日在线发表在《细胞—代谢》杂志上。

研究人员在转录和功能层面上对小鼠早期与晚期的皮肤伤口巨噬细胞进行了分析。结果表明，早期阶段的糖酵解代谢并不足以确保生产性修复。相反，通过将电子运输链的条件性破坏与tgcqmitochondrial aspartyl-tRNA合成酶的缺失相结合，然后进行单细胞测序分析，研究人员发现早期阶段的伤口巨噬细胞亚群以线粒体ROS（mtROS）的产生和HIF1α的稳定为标志，这最终驱动了对及时愈合至关重要的促血管生成程序。

相反，晚期的、有利于伤口愈合的巨噬细胞则以IL-4Rα介导的线粒体呼吸和有丝分裂为标志。总之，研究人员发现线粒体代谢的变化是伤口愈合期间巨噬细胞效应功能的一个关键控制机制。

据介绍，伤口愈合是一个协调的过程，最初依赖于促炎症的巨噬细胞，然后是这些细胞的促解功能。细胞代谢的变化可能决定了这些不同的活动，但这些变化的性质一直不清楚。

附：英文原文

Title: Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing

Author: Sebastian Willenborg, David E. Sanin, Alexander Jais, Xiaolei Ding, Thomas Ulas, Julian Nüchel, Milica Popovi, Thomas MacVicar, Thomas Langer, Joachim L. Schultze, Alexander Gerbaulet, Axel Roers, Edward J. Pearce, Jens C. Brüning, Aleksandra Trifunovic, Sabine A. Eming

Issue&Volume: 2021-10-28

Abstract: 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 tgcqmitochondrial 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 HIF1α stabilization, which ultimately drives a pro-angiogenic program essential for timely healing. In contrast, late-phase, pro-resolving wound macrophages are marked by IL-4Rα-mediated mitochondrial respiration and mitohormesis. Collectively, we identify changes in mitochondrial metabolism as a critical control mechanism for macrophage effector functions during wound healing.

DOI: 10.1016/j.cmet.2021.10.004

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00482-4 

期刊信息

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：22.415
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