氨诱导了激活的肝星细胞的亡,通过内分泌网膜压力相关的线粒体亡途径激活肝星细胞
Zhongshang Sun1,2,3,4, Yuecheng Guo3,4, Xianjun Xu3,4
1Department of Gastroenterology, Shanghai General Hospital of Nanjing Medical University, Shanghai, China.
Journal of gastroenterology and hepatology
|May 28, 2024
概括
氨 (HDD) 通过激活内质网膜应激 (ERS) 和线粒体通路,诱导激活的肝星细胞 (aHSC) 中的亡. 这种机制有助于HDD.
科学领域:
- 肝病学和分子生物学
- 纤维化细胞和分子机制.
背景情况:
- 海德罗尼 (HDD) 是皮尔芬尼的衍生物,在治疗肝纤维化方面显示出潜在的潜力.
- 对于HDD减轻肝纤维化的精确机制,尚不完全理解.
- 以前的研究表明,HDD在动物和人类肝纤维化模型中的有效性.
研究的目的:
- 为了阐明HDD抗纤维效应的机制.
- 调查HDD是否会在激活的肝星细胞 (aHSCs) 中诱导亡.
- 为了确定HDD是否利用与Endoplasmic reticulum压力 (ERS) 相关的线粒体亡途径.
主要方法:
- 在体内利用四化碳 (CCl4) 和3,5-二氧化碳-1,4-二聚氨酸 (DDC) 诱导的肝纤维化模型.
- 通过使用人类肝脏星状细胞系LX-2进行了体外研究.
- 通过TUNEL和流细胞计评估aHSC亡;用于基因沉默的siRNA.
主要成果:
- 在体内和体外模型中,HDD治疗显著增加了aHSCs的亡.
- 高强度硬盘触发了内等质网膜应激 (ERS) 并激活了IRE1α-ASK1-JNK通路.
- 被诱导的线粒体功能障碍,由细胞染色体c释放证明,导致了亡.
结论:
- 通过与ERS相关的线粒体通路,HDD会诱导激活的肝星细胞 (aHSC) 中的亡.
- 这种亲亡机制是HDD肝脏抗纤维化作用的关键贡献者.
- 这些发现支持HDD作为肝纤维化的潜在治疗剂.
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