Macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury.
Macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury.
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DOI：
10.1038/s41598-021-88989-9
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发表时间：
2021-05-06
影响因子：
4.6
通讯作者：
Seki T
中科院分区：
文献类型：
--
作者：
Miura A;Hosono T;Seki T
肝脏是一个独特的器官，具有巨大的再生能力。肝脏代谢功能表现出空间异质性，反映了肝脏分区。再生过程中控制肝细胞增殖和伴随的基质重建的机制已被很好地探索，但肝损伤后分化的代谢功能和分区的恢复潜力仍不清楚。我们采用四氯化碳（CCl4）诱导的急性肝损伤与氯膦酸盐诱导的巨噬细胞耗竭的小鼠模型，以澄清肝损伤对肝脏代谢和代谢功能的恢复动力学和再生过程中的肝脏分区的影响。消耗巨噬细胞抑制肝损伤后再生过程中的组织重塑和部分延迟细胞增殖。此外，通过抑制由耗尽的巨噬细胞引起的组织重塑，代谢功能的恢复被延迟。该模型显示，药物代谢功能对肝损伤引起的功能障碍具有弹性，但谷氨酰胺合成没有。代谢组学分析表明，肝脏支链氨基酸（BCAA）和碳水化合物代谢受到抑制损伤。血浆BCAA浓度反映再生过程中肝功能的恢复情况。我们的研究揭示了急性肝损伤后肝脏代谢再生机制的一个方面。
The liver is an exclusive organ with tremendous regenerative capacity. Liver metabolic functions exhibit spatial heterogeneity, reflecting liver zonation. The mechanisms controlling the proliferation of hepatocytes and the accompanying matrix reconstruction during regeneration have been well explored, but the recovery potential of differentiated metabolic functions and zonation after liver injury remains unclear. We employed a mouse model of carbon tetrachloride (CCl4) induced-acute liver injury with clodronate-induced macrophage depletion to clarify the impact of liver injury on liver metabolism and recovery dynamics of metabolic function and liver zonation during regeneration. Depleting macrophages suppressed tissue remodelling and partially delayed cell proliferation during regeneration after liver injury. In addition, recovery of metabolic functions was delayed by suppressing the tissue remodelling caused by the depleted macrophages. The model revealed that drug metabolic function was resilient against the dysfunction caused by liver injury, but glutamine synthesis was not. Metabolomic analysis revealed that liver branched-chain amino acid (BCAA) and carbohydrate metabolism were suppressed by injury. The plasma BCAA concentration reflected recovery of hepatic function during regeneration. Our study reveals one aspect of the regenerative machinery for hepatic metabolism following acute liver injury.
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影响因子：
64.8
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Halpern KB;Shenhav R;Matcovitch-Natan O;Toth B;Lemze D;Golan M;Massasa EE;Baydatch S;Landen S;Moor AE;Brandis A;Giladi A;Avihail AS;David E;Amit I;Itzkovitz S
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5.5
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Ju, Cynthia