Data_Sheet_1_Stimulation of Non-canonical NF-κB Through Lymphotoxin-β-Receptor Impairs Myogenic Differentiation and Regeneration of Skeletal Muscle.PDF

Myogenic differentiation, muscle stem cell functionality, and regeneration of skeletal muscle are cellular processes under tight control of various signaling pathways. Here, we investigated the role of non-canonical NF-κB signaling in myogenic differentiation, muscle stem cell functionality, and regeneration of skeletal muscle. We stimulated non-canonical NF-κB signaling with an agonistically acting antibody of the lymphotoxin beta receptor (LTβR). Interestingly, we found that stimulation of non-canonical NF-κB signaling through the LTβR agonist impairs myogenic differentiation, muscle stem cell function, and regeneration of skeletal muscle. Furthermore, we show that stimulation of non-canonical NF-κB signaling by the LTβR agonist coincides with activation of canonical NF-κB signaling. We suggest a direct crosstalk between canonical and non-canonical NF-κB signaling during myogenic differentiation which is required for proper myogenic differentiation and thereby regeneration of skeletal muscle.

肌源分化、肌肉干细胞功能及骨骼肌的再生是受到多种信号通路严格调控的细胞过程。本研究中，我们探讨了非典型性NF-κB信号通路在肌源分化、肌肉干细胞功能及骨骼肌再生中的作用。通过淋巴毒素β受体（LTβR）的激动性抗体刺激非典型性NF-κB信号通路。有趣的是，我们发现通过LTβR激动剂激活非典型性NF-κB信号通路会损害肌源分化、肌肉干细胞功能及骨骼肌的再生。此外，我们观察到，由LTβR激动剂触发的非典型性NF-κB信号通路的激活与典型性NF-κB信号通路的激活相一致。我们提出，在肌源分化过程中，典型性及非典型性NF-κB信号通路之间存在直接交互作用，这一交互作用对于肌源分化的正确进行以及骨骼肌再生的实现是必需的。