通过酒精激活肠内源逆转录病毒会加剧肝脏疾病
Noemí Cabré1, Marcos F Fondevila1, Wenchao Wei1
1Department of Medicine, UCSD, La Jolla, United States of America.
The Journal of clinical investigation
|May 13, 2025
概括
酒精消费会在肠道中触发内源逆转录病毒 (ERV),导致细胞死亡和肝脏疾病. 针对这种ERV-Zbp1通路可能为与酒精有关的肝病提供新的治疗方法.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
背景情况:
- 酒精相关性肝病 (ALD) 是一个主要的全球健康问题.
- 肠道失调和细菌转移是ALD病变发生的关键因素.
- 在酒精相关性肝炎患者中观察到复原病毒的丰度增加.
研究的目的:
- 研究内源逆转录病毒 (ERV) 在ALD发展中的作用.
- 探索乙醇诱导肠道屏障功能障碍和肝损伤的机制.
主要方法:
- 来自ALD患者的十二指肠和肝脏活检的转录组分析.
- 在老鼠中慢性饮食过多的乙醇食,以评估ERV诱导和信号通路.
- 在小鼠模型中使用抗逆转录病毒治疗和基因删除 (Zbp1).
- 评估肠道屏障完整性和肝脏病理.
主要成果:
- 在ALD患者中增加人体ERVs (HERV-K,HERV-H) 的表达.
- 乙醇食诱导了小鼠肠道细胞中的ERV丰富性,激活了Zbp1-Mlkl亡途径.
- 在小鼠中,抗逆转录病毒治疗减少了ERV表达,改善了肠道屏障,并减少了肝病.
- 肠特异性Zbp1删除保护小鼠免受细菌转移和脂肪肝炎.
结论:
- 乙醇诱导ERV并促进先天性免疫反应,导致肠上皮细胞死亡,肠道屏障功能障碍和ALD.
- ERV-Zbp1通路是乙醇诱导的肝损伤的关键调解者.
- 准ERV-Zbp1通路为ALD提供了一个潜在的治疗策略.
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