通过Ca2+/NF-B/LECT2通路破坏肝细胞,ITPR3促进肝纤维化
Xiaojuan Zhao1, Xue Liu2, Min Ni2
1School of Pharmacy, Yancheng Teachers University, No.2, Xiwang South Road, Tinghu District (224007), Yancheng, 224007, Jiangsu, P. R. China. zhaoxj@yctu.edu.cn.
Scientific reports
|March 14, 2026
概括
伊诺西1,4,5-三酸盐受体3型 (ITPR3) 的新表达通过激活Ca2+/NF-κB/LECT2通路驱动肝纤维化,导致肝细胞损伤和亡. 抑制ITPR3可以治疗肝纤维化.
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
- 细胞病理学细胞病理学
背景情况:
- 肝细胞损伤引发肝损伤,新型内醇1,4,5-三酸盐受体3型 (ITPR3) 表达与肝细胞癌相关.
- 在肝细胞驱动性肝纤维化中ITPR3表达的特异性作用仍然在很大程度上未被描述.
研究的目的:
- 调查肝纤维化期间肝细胞中ITPR3表达的 de novo作用.
- 阐明涉及Ca2+/核因子-κB (NF-κB) /白细胞细胞衍生的化学毒素2 (LECT2) 途径的潜在分子机制.
主要方法:
- 在肝细胞和纤维化小鼠肝脏中分析ITPR3的表达.
- 对Ca2+/NF-κB/LECT2通路激活的评估.
- 在体内和体外使用ITPR3siRNA和NF-κB抑制剂对肝细胞损伤和肝纤维化的ITPR3影响的评估.
主要成果:
- 在四化碳诱导的纤维性肝脏和肝细胞中,ITPR3的表达显著增加,与肝细胞亡相关.
- 由ITPR3介导的过度Ca2+释放激活了NF-κB,导致LECT2表达,肝细胞亡,以及随后的肝星细胞激活.
- 确定ITPR3表达是肝细胞损伤和肝纤维化进展的关键因素.
结论:
- 通过Ca2+/NF-κB/LECT2通路,ITPR3表达在肝细胞损伤和肝纤维化中起着关键作用.
- 向ITPR3为缓解肝纤维化和相关的肝细胞损伤提供了潜在的治疗策略.
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