肝细胞特异性表皮生长因子受体 (EGFR) 缺失减弱了小鼠中乙氨基诱导的肝损伤
Siddhi Jain1,2, Gillian Williams1,2, Ranjan Mukherjee1,2
1Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
概括
在肝细胞中删除表皮生长因子受体 (EGFR) 通过减少细胞死亡和增强修复机制,意外地阻止了乙氨基诱导的肝损伤进展.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
- 毒理学 毒理学 毒理学
背景情况:
- 皮表皮生长因子受体 (EGFR) 主要因其在肝细胞增殖中的作用而得到认可.
- 之前的研究表明EGFR在促进乙氨基诱导肝损伤 (AILI) 模型中的细胞死亡方面具有矛盾的功能.
研究的目的:
- 调查EGFR在恶化AILI中的意想不到的作用.
- 阐明EGFR影响肝损伤和再生的机制.
主要方法:
- 使用AAV8.TBG.Cre和EGFRfl/fl小鼠生成肝细胞特异性EGFR缺乏的小鼠.
- 使用毒性剂量的乙氨基 (500 mg/kg) 诱导肝损伤.
- 评估肝损伤,再生和信号通路在各种时间点后的乙氨基暴露.
主要成果:
- EGFR缺失没有影响最初的肝损伤,但在12小时和24小时后明显减轻了损伤的进展.
- EGFR缺乏限制了长时间的JNK激活,线粒体损伤和细胞死亡.
- 在EGFR缺乏的小鼠中,通过TFEB观察到更快的谷氨 (GSH) 补充和自的上调.
- EGFR的删除促进了补偿性肝细胞的增殖.
结论:
- 肝细胞特异性EGFR缺失可以阻止乙氨基诱导的肝损伤的进展.
- 在促进AILI进展方面,EGFR起着意想不到的作用,影响肝脏生物学和治疗策略.
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