Increased expression of atrogenes and TWEAK family members after severe burn injury in nonburned human skeletal muscle.
Increased expression of atrogenes and TWEAK family members after severe burn injury in nonburned human skeletal muscle.
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DOI：
10.1097/bcr.0b013e31827a2a9c
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发表时间：
2013-09
期刊：
影响因子：
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通讯作者：
Bamman MM
中科院分区：
文献类型：
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作者：
Merritt EK;Thalacker-Mercer A;Cross JM;Windham ST;Thomas SJ;Bamman MM
严重烧伤会在受伤后引起骨骼肌快速蛋白水解，这种情况持续长达一年，尽管采取了饮食和康复干预措施，仍会导致骨骼肌萎缩。本研究的目的是确定烧伤后骨骼肌质量调节基因表达的急性变化。在烧伤后 5.1 ± 1.1 天，从 8 名烧伤受试者（6M，2F：34.8 ± 2.7 岁：29.9 ± 3.1% 全身表面积烧伤）的未烧伤腿的股外侧肌和匹配对照中获取活组织检查。测定肿瘤坏死因子-α (TNF-α) 和白介素-6 (IL-6) 家族中细胞因子和受体以及泛素蛋白酶体 E3 连接酶、atrogin-1 和 MuRF1 的 mRNA 表达。烧伤时 TNF 受体 1A 的浓度增加了 3.5 倍以上。烧伤后TNF样弱凋亡诱导剂及其受体的表达分别升高1.6倍和6.0倍以上。在具有 IL-6 受体的烧伤受试者中，IL-6、IL-6 受体和糖蛋白 130 升高超过 13 倍。烧伤时细胞因子信号传导抑制因子 3 也升高了近 6 倍。 Atrogin-1 和 MuRF1 的烧伤程度分别高出 4 倍和 3 倍以上。这些结果首次证明，人类严重烧伤对未烧伤肢体骨骼肌中促进炎症和蛋白水解的基因表达有显着影响。由于这些变化可能会导致未直接受烧伤影响的区域发生急性骨骼肌萎缩，因此未来确定负责的系统线索将非常重要。
Severe burn induces rapid skeletal muscle proteolysis after the injury that persists for up to one year and results in skeletal muscle atrophy despite dietary and rehabilitative interventions. The purpose of this research was to determine acute changes in gene expression of skeletal muscle mass regulators post-burn injury. Biopsies were obtained from the vastus lateralis of a non-burned leg of eight burned subjects (6M, 2F: 34.8 ± 2.7 years: 29.9 ± 3.1% total body surface area burn) at 5.1 ± 1.1 days post-burn injury and from matched controls. mRNA expression of cytokines and receptors in the tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) families, and the ubiquitin proteasome E3 ligases, atrogin-1 and MuRF1, was determined. TNF receptor 1A was over 3.5 fold higher in burn. Expression of TNF-like weak inducer of apoptosis and its receptor were over 1.6 and 6.0-fold higher in burn. IL-6, IL-6 receptor, and glycoprotein 130, were elevated in burned subjects with IL-6 receptor over 13-fold higher. Suppressor of cytokine signaling-3 was also elevated in burn nearly 6-fold. Atrogin-1 and MuRF1, were more than 4- and 3-fold higher in burn. These results demonstrate for the first time that severe burn in humans has a remarkable impact on gene expression in skeletal muscle of a non-burned limb of genes that promote inflammation and proteolysis. Because these changes likely contribute to the acute skeletal muscle atrophy in areas not directly affected by the burn, in the future it will be important to determine the responsible systemic cues.