RelA通过协调调节一个新的Myogenin远端增强器来抑制胚胎肌发生
Md Nazmul Hossain1, Yao Gao1, Sharmeen Islam1
1Nutrigenomics and Growth Biology Laboratory, Pullman, WA, 99164, USA.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|July 28, 2025
概括
孕产妇的肥胖会通过降低myogenin (Myog) 的调节来损害胚胎肌肉发育. 炎症因子RelA向一个Myog增强剂,抑制肌肉生成. 甲胺治疗可以逆转这些影响.
科学领域:
- 发育生物学是发展生物学.
- 分子生物学分子生物学
- 代谢健康 代谢健康
背景情况:
- 骨肌肉的发育对于终身代谢健康至关重要.
- 孕产妇的肥胖会对胚胎肌体发生产生负面影响,特别是肌管的形成.
- 肌原蛋白 (Myog) 表达对于肌原生成至关重要,并且在肥胖母亲的胚胎中是下调的.
研究的目的:
- 为了研究母体肥胖症损害胚胎肌发生的分子机制.
- 确定RelA的作用及其与Myog基因增强剂的相互作用.
- 探索治疗干预措施,以缓解肥胖引起的发育缺陷.
主要方法:
- 单细胞RNA测序和空间转录组学用于分析胚胎组织中的基因表达.
- 单细胞ATAC测序以识别调控元素和转录因子结合.
- 在体外实验中涉及RelA敲击和抑制的实验.
- 在体内研究中,在肥胖小鼠模型中使用甲福明治疗.
主要成果:
- 孕产妇的肥胖导致胚胎的Myog表达减少和肌管形成受损.
- 炎症转录因子RelA在肥胖胚胎的肌细胞中被上调.
- RelA与远端Myog增强剂结合,从而抑制Myog表达和肌细胞形成.
- 在体外RelA抑制和体内甲福林治疗恢复了Myog表达和肌肉形成.
结论:
- 远端Myog增强剂的RelA介导抑制是导致母体肥胖诱导的胚胎肌形成缺陷的关键机制.
- 准RelA信号提供了一个潜在的治疗策略,以抵消由母亲肥胖引起的发育障碍.
- 了解这些分子通路对于促进骨肌肉发育和从胚胎发生开始的代谢健康至关重要.
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