NF-κB-induced loss of MyoD messenger RNA:: Possible role in muscle decay and cachexia
NF-κB-induced loss of MyoD messenger RNA:: Possible role in muscle decay and cachexia
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DOI：
10.1126/science.289.5488.2363
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发表时间：
2000-09-29
期刊：
影响因子：
56.9
通讯作者：
Baldwin, AS
中科院分区：
文献类型：
--
作者：
Guttridge, DC;Mayo, MW;Baldwin, AS
MyoD调节骨骼肌分化（SMD），对受损组织的修复至关重要。转录因子核因子κ B（NF-κ B）被细胞因子肿瘤坏死因子（TNF）激活，肿瘤坏死因子是恶病质中骨骼肌萎缩的介质。在分化的C2 C12肌细胞中，TNF诱导的NF-κ B活化通过在转录后水平抑制MyoD mRNA来抑制SMD。相反，在分化的肌管中，TNF加干扰素-γ（IFN-γ）信号传导是需要NF-κ B依赖性MyoD下调和骨骼肌纤维功能障碍。在体内小鼠肌肉中，TNF和IFN-γ表达也下调MyoD mRNA。这些数据阐明了恶病质中骨骼肌衰退的可能机制。
MyoD regulates skeletal muscle differentiation (SMD) and is essential for repair of damaged tissue. The transcription factor nuclear factor kappa B (NF-kappa B) is activated by the cytokine tumor necrosis factor (TNF), a mediator of skeletal muscle wasting in cachexia, Here, the role of NF-kappa B in cytokine-induced muscle degeneration was explored. In differentiating C2C12 myocytes, TNF-induced activation of NF-kappa B inhibited SMD by suppressing MyoD mRNA at the post-transcriptional level. In contrast, in differentiated myotubes, TNF plus interferon-gamma (IFN-gamma) signaling was required for NF-kappa B-dependent down-regulation of MyoD and dysfunction of skeletal myofibers. MyoD mRNA was also down-regulated by TNF and IFN-gamma expression in mouse muscle in vivo. These data elucidate a possible mechanism that may underlie the skeletal muscle decay in cachexia.