逐渐的DNA甲基化变化揭示了与代谢功能障碍相关的脂肪性肝病进展和表观遗传衰老加速有关的转录因子
Evelien Van Dijck1,2, Steven Van Laere3, Emilie Logie4
1Cell Death Signaling-Epigenetics Lab, Department Biomedical Sciences, University of Antwerp, 2610, Wilrijk, Belgium. evelien.vandijck@uantwerpen.be.
Clinical epigenetics
|August 5, 2025
概括
DNA甲基化变化跟踪了代谢功能障碍相关的脂肪性肝病 (MASLD) 的进展和表观遗传衰老加速 (EAA). EAA可以作为MASLD的生物标志物,识别新的治疗点.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 肝脏疾病的发病因子 肝脏疾病的发病因子
- 衰老研究研究 衰老研究
背景情况:
- 与代谢功能障碍相关的脂肪性肝病 (MASLD) 是一种普遍存在的全球性肝病,其机制尚不清楚.
- 衰老与MASLD共享炎症和氧化应激过程.
- 基因甲基化 (DNAm) 失调与MASLD的发病和衰老有关.
研究的目的:
- 为了研究与MASLD进展有关的DNA甲基化 (DNAm) 变化.
- 探索MASLD与表观遗传衰老加速 (EAA) 之间的关联.
- 通过综合性分析来确定潜在的治疗点.
主要方法:
- 使用MethylationEPIC BeadChip数组分析了22名不同MASLD状态的个体的肝脏活检.
- 对EAA (Horvath's,LiverClock,内在,HepClock) 与MASLD阶段和组织学的相关性分析.
- 对DNAm,基因表达 (n=118) 和一个MASLD特定的转录调节网络的综合分析.
主要成果:
- MASLD的进展与逐渐的DNAm变化相关,并影响了多个KEGG通路.
- 霍瓦斯的EAA与MASLD阶段和组织学参数有显著的相关性;LiverClock的EAA与MASLD阶段有显著的相关性.
- 综合性分析确定了参与与MASLD和EAA相关的氧化还原,免疫和代谢过程的转录因子.
结论:
- 渐进的DNAm变化与MASLD进展和EAA一致,表明EAA是潜在的生物标志物.
- 综合性分析揭示了潜在的治疗转录因子标,包括AEBP1和核受体.
- 表观遗传氧化还原代谢疗法对MASLD治疗具有前景.
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