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甲状腺激素受体α调节肝脏恒星细胞中的纤维生成
Paul Manka1,2, Jason D Coombes3, Svenja Sydor1
1Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
概括
甲状腺激素 (TH) 通过与肝脏恒星细胞中的TH受体α (TRα) 相互作用来调节肝纤维化. TRα信号会抑制纤维基因表达,这表明TH-TR轴是肝纤维化的治疗点.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 渐进性肝纤维化是慢性肝病的末期阶段,肝星细胞 (HSC) 是纤维生成的核心.
- 甲状腺激素 (TH),包括甲状腺素 (T4) 和三甲状腺素 (T3),通过TH受体 (TRα/β) 调节细胞过程.
研究的目的:
- 为了研究TH对肝纤维生成的影响.
- 阐明TRα在调解TH对HSC激活和肝纤维化的作用中的作用.
主要方法:
- 使用人类肝脏实验剂和TRα缺乏 (TRα-KO) 和野生型 (WT) 控制或甲氨酸胆缺乏 (MCD) 饮食的小鼠.
- 纤维基因标记物的基因表达通过qRT-PCR进行了评估.
- 试验室研究涉及用TGFβ和T3治疗HSC,并使用TRα淘汰/缺乏细胞.
主要成果:
- 在纤维化人类和小鼠肝脏中,TRα和TRβ的表达减少;TRα在HSC中占主导地位.
- 在体外,T3抑制了TGFβ诱导的纤维化基因表达和依赖TRα的HSC激活.
- TRα-KO小鼠表现出恶化的MCD饮食引起的肝纤维化.
结论:
- 对于肝脏纤维化来说,TH在非辅酶细胞,特别是HSC中的作用至关重要.
- TH-TRα轴通过TGFβ信号通路调节HSC表型.
- 准TH-TR轴为肝纤维化提供了一个潜在的治疗策略.
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