RUNX1通过激活JUNB/NF-κB通路并驱动M1巨细胞两极分化来促进脱神经诱导的肌肉缩
Wei Hu1, Yang Huang1, Wei Yin1
1Department of Radiology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, No. 228, Jingui Road, Xian'an District, Xianning, Hubei, 437000, China.
Open life sciences
|September 8, 2025
概括
转录因子RUNX1通过激活JUNB和NF-κB通路,驱动神经损伤后的炎症和肌肉缩. 准这个RUNX1-JUNB-NF-κB轴可以治疗肌肉退化.
科学领域:
- 肌肉生物学 肌肉生物学
- 神经免疫学 神经免疫学
- 分子生物学分子生物学
背景情况:
- 周围神经损伤通过慢性炎症和改变巨细胞功能导致肌肉缩.
- 转录因子RUNX1在无神肌肌肉中被上调,但其在缩和炎症中的作用尚未完全理解.
研究的目的:
- 为了研究RUNX1-JUNB-NF-κB信号轴在调节炎症介导的肌肉缩后化.
- 为了确定RUNX1的下游点,参与炎症反应和肌肉退化.
主要方法:
- 对单核RNA测序数据 (GSE183802) 和小鼠坐骨神经切割模型的分析.
- 染色体免疫沉,双露西法酶记者测定和siRNA敲击来研究JUNB的RUNX1调节.
- 在体外研究中使用C2C12神经管和RAW 264.7巨细胞来评估炎症反应和NF-κB激活.
主要成果:
- 在无神肌肌肉中,RUNX1被上调,并与缩标志物 (MuRF1,Atrogin-1) 相相关.
- RUNX1直接激活了JUNB转录,导致NF-κB通路激活和M1巨细胞极化 (增加IL-1β,TNF-α).
- 关闭JUNB消除了RUNX1诱导的炎症,NF-κB信号传递和肌肉缩标志物.
结论:
- RUNX1-JUNB-NF-κB轴是炎症驱动的肌肉缩的关键调节者.
- 这一途径代表了一种潜在的治疗标,用于减轻外围神经损伤和运动神经元疾病中的神经性肌肉退化和免疫介导损伤.
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