小柯机器人

巨噬细胞可分泌谷氨酰胺来促进肌肉再生
2020-10-29 16:13

比利时鲁汶大学Massimiliano Mazzone、Emanuele Berardi等研究人员合作发现,巨噬细胞来源的谷氨酰胺可促进卫星细胞和肌肉再生。该项研究成果于2020年10月28日在线发表在《自然》杂志上。

研究人员发现,在小鼠模型中,肌肉损伤和衰老的特征在于组织内谷氨酰胺的限制。低水平的谷氨酰胺使得巨噬细胞通过谷氨酰胺合成酶(GS)活性增强从而具有分泌谷氨酰胺的代谢能力,但以谷氨酸脱氢酶1(GLUD1)介导的谷氨酰胺氧化为代价。Glud1基因敲除的巨噬细胞显示出高组成型的GS活性,可防止谷氨酰胺短缺。卫星细胞通过谷氨酰胺转运蛋白SLC1A5摄取巨噬细胞来源的谷氨酰胺可激活mTOR,并促进卫星细胞的增殖和分化。因此,巨噬细胞特异性的GLUD1缺失或药理抑制作用可改善对急性损伤、局部缺血或衰老的肌肉再生和功能恢复。
 
相反,卫星细胞中的SLC1A5阻断或巨噬细胞中的GS失活会对卫星细胞功能和肌肉再生产生负面影响。这些结果突出了卫星细胞与巨噬细胞之间的代谢交流,即巨噬细胞来源的谷氨酰胺维持了卫星细胞的功能。因此,靶向GLUD1可以为受伤或衰老的肌肉再生提供治疗机会。
 
研究人员介绍,巨噬细胞浸润以及随后的卫星细胞激活可维持肌肉再生。巨噬细胞和卫星细胞以不同的方式进行交流,但尚未研究它们的代谢相互作用。
 
附:英文原文

Title: Macrophage-derived glutamine boosts satellite cells and muscle regeneration

Author: Min Shang, Federica Cappellesso, Ricardo Amorim, Jens Serneels, Federico Virga, Guy Eelen, Stefania Carobbio, Melvin Y. Rincon, Pierre Maechler, Katrien De Bock, Ping-Chih Ho, Marco Sandri, Bart Ghesquire, Peter Carmeliet, Mario Di Matteo, Emanuele Berardi, Massimiliano Mazzone

Issue&Volume: 2020-10-28

Abstract: Muscle regeneration is sustained by infiltrating macrophages and the consequent activation of satellite cells1,2,3,4. Macrophages and satellite cells communicate in different ways1,2,3,4,5, but their metabolic interplay has not been investigated. Here we show, in a mouse model, that muscle injuries and ageing are characterized by intra-tissue restrictions of glutamine. Low levels of glutamine endow macrophages with the metabolic ability to secrete glutamine via enhanced glutamine synthetase (GS) activity, at the expense of glutamine oxidation mediated by glutamate dehydrogenase 1 (GLUD1). Glud1-knockout macrophages display constitutively high GS activity, which prevents glutamine shortages. The uptake of macrophage-derived glutamine by satellite cells through the glutamine transporter SLC1A5 activates mTOR and promotes the proliferation and differentiation of satellite cells. Consequently, macrophage-specific deletion or pharmacological inhibition of GLUD1 improves muscle regeneration and functional recovery in response to acute injury, ischaemia or ageing. Conversely, SLC1A5 blockade in satellite cells or GS inactivation in macrophages negatively affects satellite cell functions and muscle regeneration. These results highlight the metabolic crosstalk between satellite cells and macrophages, in which macrophage-derived glutamine sustains the functions of satellite cells. Thus, the targeting of GLUD1 may offer therapeutic opportunities for the regeneration of injured or aged muscles.

DOI: 10.1038/s41586-020-2857-9

Source: https://www.nature.com/articles/s41586-020-2857-9

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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