Maresin1 alleviates liver ischemia/reperfusion injury by reducing liver macrophage pyroptosis.
Maresin1 alleviates liver ischemia/reperfusion injury by reducing liver macrophage pyroptosis.
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DOI：
10.1186/s12967-023-04327-9
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发表时间：
2023-07-16
影响因子：
7.4
通讯作者：
Zhu, Peng
中科院分区：
文献类型：
--
作者：
Li, Tong;Zeng, Houshuai;Xian, Wenjing;Cai, Hongxing;Zhang, Jianbo;Zhou, Shiji;Yang, Yingxue;Luo, Min;Zhu, Peng
细胞下垂具有很强的促炎作用，但目前尚不清楚肝巨噬细胞下垂是否加重了肝脏缺血再灌注损伤中的肝组织损伤。Maresin1(MaR1)具有较强的抗炎作用，是否能抑制肝巨噬细胞下垂尚需进一步研究。本研究旨在探讨MaR1能否通过抑制巨噬细胞松弛来减轻肝脏I/R损伤。将细胞分为对照组、缺氧/复氧组和缺氧/复氧 + 组，观察其对细胞松弛和线粒体损伤的影响。用敲除RORA的方法研究了MaR1发挥保护作用的机制。采用转录组分析、定量逆转录聚合酶链式反应和Western blotting分析基因表达。使用非靶向代谢组学技术分析小鼠的代谢物图谱。用流式细胞术检测细胞死亡和线粒体损伤。我们首次发现MaR1显著减轻肝脏I/R损伤。我们观察到MaR1通过抑制肝巨噬细胞下垂来减轻肝脏I/R损伤。随后，我们发现MaR1促进了线粒体氧化磷酸化，增加了ATP的合成，减少了ROS的产生，减轻了线粒体膜电位的损伤，抑制了线粒体膜通透性转换孔的开放。MaR1通过保护线粒体来抑制肝巨噬细胞的嗜热症。最后，我们发现MaR1通过激活其核受体RORA和PI3K/AKT信号通路发挥线粒体保护作用。在肝脏I/R损伤过程中，MaR1可通过减少线粒体损伤来减少肝巨噬细胞的嗜酸血症，从而减轻肝脏损伤。网上版载有补充材料，可在10.1186/s12967-023-04327-9查阅。
Cell pyroptosis has a strong proinflammatory effect, but it is unclear whether pyroptosis of liver macrophages exacerbates liver tissue damage during liver ischemia‒reperfusion (I/R) injury. Maresin1 (MaR1) has a strong anti-inflammatory effect, and whether it can suppress liver macrophage pyroptosis needs further study. This study aimed to investigate whether MaR1 can alleviate liver I/R injury by inhibiting macrophage pyroptosis. The effects of MaR1 on cell pyroptosis and mitochondrial damage were studied by dividing cells into control, hypoxia/reoxygenation, and hypoxia/reoxygenation + MaR1 groups. Knocking out RORa was used to study the mechanism by which MaR1 exert its protective effects. Transcriptome analysis, qRT‒PCR and Western blotting were used to analyze gene expression. Untargeted metabolomics techniques were used to analyze metabolite profiles in mice. Flow cytometry was used to assess cell death and mitochondrial damage. We first found that MaR1 significantly reduced liver I/R injury. We observed that MaR1 decreased liver I/R injury by inhibiting liver macrophage pyroptosis. Then, we discovered that MaR1 promotes mitochondrial oxidative phosphorylation, increases the synthesis of ATP, reduces the generation of ROS, decreases the impairment of mitochondrial membrane potential and inhibits the opening of mitochondrial membrane permeability transition pores. MaR1 inhibits liver macrophage pyroptosis by protecting mitochondria. Finally, we found that MaR1 exerts mitochondrial protective effects through activation of its nuclear receptor RORa and the PI3K/AKT signaling pathway. During liver I/R injury, MaR1 can reduce liver macrophage pyroptosis by reducing mitochondrial damage, thereby reducing liver damage. The online version contains supplementary material available at 10.1186/s12967-023-04327-9.
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影响因子：
7.4
作者：
Chi X;Wei X;Gao W;Guan J;Yu X;Wang Y;Li X;Cai J
通讯作者：
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影响因子：
24.1
作者：
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作者：
Xian, Wenjing;Li, Tong;Cao, Jun
通讯作者：
Cao, Jun
DOI：
10.1016/j.jcmgh.2021.11.009
发表时间：
2022
影响因子：
7.2
作者：
Sun P;Zhong J;Liao H;Loughran P;Mulla J;Fu G;Tang D;Fan J;Billiar TR;Gao W;Scott MJ
通讯作者：
Scott MJ
影响因子：
16
作者：
Planes, Remi;Pinilla, Miriam;Santoni, Karin;Hessel, Audrey;Passemar, Charlotte;Lay, Kenneth;Paillette, Perrine;Valadao, Ana-Luiza Chaves;Robinson, Kim Samirah;Bastard, Paul;Lam, Nathaniel;Fadrique, Ricardo;Rossi, Ida;Pericat, David;Bagayoko, Salimata;Leon-Icaza, Stephen Adonai;Rombouts, Yoann;Perouzel, Eric;Tiraby, Michele;Zhang, Qian;Cicuta, Pietro;Jouanguy, Emmanuelle;Neyrolles, Olivier;Bryant, Clare E.;Floto, Andres R.;Goujon, Caroline;Lei, Franklin Zhong;Martin-Blondel, Guillaume;Silva, Stein;Casanova, Jean-Laurent;Cougoule, Celine;Reversade, Bruno;Marcoux, Julien;Ravet, Emmanuel;Meunier, Etienne
通讯作者：
Meunier, Etienne