在肝脏再生过程中,SOX9通过上调TGF-α表达来促进肝细胞增殖
Shu-Qing Liu1,2, Hai-Lin Xiong1, Chuan Yin1
1Department of Gastroenterology, Shanghai Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai, 200003, China.
Hepatology international
|November 3, 2025
概括
肝细胞核因子4α (HNF4α) 在肝损伤期间抑制SOX9. 通过增加转化生长因子-α (TGF-α) 信号传递,SOX9促进肝细胞的增殖并增强肝脏的再生.
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
- 再生医学是一种再生医学.
背景情况:
- 肝脏具有显著的再生能力.
- SOX9和HNF4α与慢性肝损伤有关,HNF4α的删除促进了肝细胞的增殖.
- 目前尚不清楚SOX9在肝脏再生中的具体作用.
研究的目的:
- 阐明SOX9在肝脏再生中的作用.
- 调查SOX9和HNF4α之间的调控关系.
- 确定SOX9影响肝细胞增殖的分子机制.
主要方法:
- 已建立的急性肝损伤模型 (部分肝切除术,四化碳注射).
- 使用肝细胞特定的Hnf4α和Sox9淘汰/过度表达的小鼠模型.
- 进行RNA测序和共同培养实验,以评估分子途径.
主要成果:
- 在急性肝损伤期间,SOX9表达增加,而HNF4α减少.
- 通过miR-124/381.1,HNF4α通过SOX9进行负调节.
- 缺失SOX9会影响肝脏的再生,而过度表达SOX9会改善存活率和繁殖率.
- SOX9通过调节TGF-α来促进肝细胞的增殖,TGF-α激活了EGFR信号传递.
结论:
- 在肝细胞中,HNF4α负面调节SOX9的表达.
- SOX9对于促进肝细胞增殖和增强肝脏再生至关重要.
- 在肝脏修复过程中,TGF-α信号调解SOX9的增殖效应.
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