EP300/YAP1-SERPINE1 信号调节胆道动脉动脉症中状反应和肝纤维化
Zhongxian Zhu1, Changgui Lu1, Xiaofeng Lv1
1Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
Cellular and molecular gastroenterology and hepatology
|September 24, 2025
概括
胆道动脉缩 (BA) 涉及状反应和肝纤维化. 向EP300/YAP1-SERPINE1通路显示了治疗BA.婴儿进步性肝纤维化的潜力.
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
- 儿科胃肠病学 儿科胃肠病学
背景情况:
- 胆管缩 (BA) 是婴儿胆固醇性肝病的主要原因.
- BA的特点是管状反应 (DR) 和肝纤维化 (LF),但潜在的机制尚不清楚.
- 这项研究研究了胆管细胞中的分子信号,这些信号有助于BA中的LF.
研究的目的:
- 阐明Yes1关联转录调节器 (YAP1) 在胆道缩中的作用.
- 为了确定参与胆细胞诱导的肝纤维化中的分子通路.
- 探索EP300作为BA肝纤维化的治疗标.
主要方法:
- 使用BA肝脏组织和细胞模型.
- 在被 rhesus 轮状病毒 (RRV) 感染的 cholangiocyte 器官 (COs) 上进行了 ATAC-seq 和 RNA-seq .
- 使用co-IP,ChIP和露西法酶试验研究了EP300/YAP1-SERPINE1通路相互作用;在RRV小鼠模型中验证了结果.
主要成果:
- 在BA胆管细胞中YAP1的上调促进了增殖,并激活了肝脏的恒星细胞.
- 确定了SERPINE1作为YAP1的目标,EP300有助于其转录.
- 在小鼠中的EP300抑制降低了DR和LF,改善了BA和RRV模型中的胆管细胞完整性.
结论:
- 这种EP300/YAP1-SERPINE1通路对于BA的DR相关性肝纤维化至关重要.
- 在BA患者中,EP300抑制对渐进性肝纤维化具有潜在的治疗策略.
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