Acute muscle mass loss was alleviated with HMGB1 neutralizing antibody treatment in severe burned rats.
Acute muscle mass loss was alleviated with HMGB1 neutralizing antibody treatment in severe burned rats.
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DOI：
10.1038/s41598-023-37476-4
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发表时间：
2023-06-24
影响因子：
4.6
通讯作者：
Garg, Nisha J.
中科院分区：
文献类型：
--
作者：
Song, Juquan;Chowdhury, Imran H.;Choudhuri, Subhadip;Ayadi, Amina E. I.;Rios, Lizette E.;Wolf, Steven E.;Wenke, Joseph C.;Garg, Nisha J.
烧伤与肌肉萎缩有关，尽管相关的信号传导机制还不清楚。在这项研究中，我们的目的是研究高迁移率族蛋白1（HMGB 1）在烧伤后过度炎症和随后的骨骼肌损伤信号中的作用。将Sprague道利大鼠随机分为3组：（1）假烧伤组，（2）烧伤组，（3）烧伤/治疗组。第2组和第3组分别给予鸡IgY和抗HMGB 1抗体治疗。伤后第3天采集肌肉组织和其他样品。烧伤大鼠的体重和后肢肌肉（总的和单独的）的湿/干重显著降低。急性烧伤引起了线粒体应激和细胞死亡，并增加了蛋白质泛素化和LC 3A/B水平，参与蛋白质降解。此外，烧伤大鼠循环和脾脏中的肌肉炎性浸润增加与骨髓髓样细胞和αβ CD 4 + T和γδ T淋巴细胞的分化、成熟和促炎性活化增加相关。用一剂HMGB 1中和抗体治疗减少了烧伤伤口的大小，并保持了与烧伤大鼠中细胞死亡和自噬途径标志物对照相关的后肢肌肉的湿/干重。此外，抗HMGB 1抗体抑制烧伤大鼠肌肉组织中的髓样和T细胞炎症激活以及随后的失调的炎症浸润。我们的结论是，HMGB 1依赖的蛋白水解和炎症反应的中和在防止严重烧伤后的肌肉损失有潜在的有益作用。
Burn injury is associated with muscle wasting, though the involved signaling mechanisms are not well understood. In this study, we aimed to examine the role of high mobility group box 1 (HMGB1) in signaling hyper-inflammation and consequent skeletal muscle impairment after burn. Sprague Dawley rats were randomly assigned into three groups: (1) sham burn, (2) burn, (3) burn/treatment. Animals in group 2 and group 3 received scald burn on 30% of total body surface area (TBSA) and immediately treated with chicken IgY and anti-HMGB1 antibody, respectively. Muscle tissues and other samples were collected at 3-days after burn. Body mass and wet/dry weights of the hind limb muscles (total and individually) were substantially decreased in burn rats. Acute burn provoked the mitochondrial stress and cell death and enhanced the protein ubiquitination and LC3A/B levels that are involved in protein degradation in muscle tissues. Further, an increase in muscle inflammatory infiltrate associated with increased differentiation, maturation and proinflammatory activation of bone marrow myeloid cells and αβ CD4+ T and γδ T lymphocytes was noted in in circulation and spleen of burn rats. Treatment with one dose of HMGB1 neutralizing antibody reduced the burn wound size and preserved the wet/dry weights of the hind limb muscles associated with a control in the markers of cell death and autophagy pathways in burn rats. Further, anti-HMGB1 antibody inhibited the myeloid and T cells inflammatory activation and subsequent dysregulated inflammatory infiltrate in the muscle tissues of burn rats. We conclude that neutralization of HMGB1-dependent proteolytic and inflammatory responses has potential beneficial effects in preventing the muscle loss after severe burn injury.
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影响因子：
7.4
作者：
Hwang PF;Porterfield N;Pannell D;Davis TA;Elster EA
通讯作者：
Elster EA
影响因子：
3.7
作者：
Charles JP;Cappellari O;Spence AJ;Hutchinson JR;Wells DJ
通讯作者：
Wells DJ
影响因子：
5.5
作者：
Haberecht-Müller S;Krüger E;Fielitz J
通讯作者：
Fielitz J
影响因子：
2.2
作者：
Song, Juquan;de Libero, Jana;Wolf, Steven E.
通讯作者：
Wolf, Steven E.
影响因子：
9
作者：
Hart, DW;Wolf, SE;Herndon, DN
通讯作者：
Herndon, DN