通过YAP信号通路,AHR调节肝脏的扩大和再生
1Lin He's Academician Workstation of New Medicine and Clinical Translation, Jining Medical University, Jining, China.
Heliyon
|September 19, 2024
概括
基碳化合物受体 (AHR) 通过激活AHR-TEAD信号通路来促进肝脏的扩大和再生. 这项研究阐明了AHR.
科学领域:
- 肝病学和分子生物学
- 细胞信号通道 细胞信号通道
- 转录因子法规转录因子法规
背景情况:
- 基碳化合物受体 (AHR) 是一种联体激活的转录因子,参与各种生理过程.
- 虽然AHR激活与肝壮病有关,但驱动肝脏扩大和再生的确切机制仍然不完全理解.
研究的目的:
- 调查AHR激活影响肝脏大小和再生的分子机制.
- 阐明AHR-TEAD信号通路在AHR介导的肝壮病和肝脏修复中的作用.
主要方法:
- 使用了转基因小鼠模型 (AHRfl/fl.ALB-CreERT2,AHRΔHep,YAPΔHep) 和部分肝切除模型.
- 用无毒的AHR配体YH439来评估对肝/体重比,肝细胞大小和细胞增殖 (Ki67) 的影响.
- 进行共免疫沉以探索AHR,YAP和TEAD之间的蛋白质-蛋白质相互作用;评估信号通路抑制.
主要成果:
- 在野生型和AHRfl/fl.ALB-CreERT2小鼠中,YH439显著增加了肝/体重比和肝细胞扩大,但在AHRΔHep小鼠中没有.
- AHR激活增加了门静脉周围的肝细胞增殖 (Ki67+),并在部分肝切除术后以AHR依赖的方式增强了肝脏再生.
- 由AHR诱导的肝脏扩大和再生取决于AHR,YAP和TEAD之间的相互作用,因为阻断这种途径或使用YAPΔHep小鼠会取消效应.
结论:
- 通过AHR-TEAD信号通路,AHR的激活驱动肝脏的扩大和再生.
- 这项研究揭示了AHR在调节肝脏平衡和修复方面的一种新机制.
- 这些发现为针对肝脏再生障碍的治疗策略提供了理论基础.
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