在肝脏巨细胞中的孕妇X受体激活可以防止内毒素诱导的肝损伤
Tingting Zhao1,2, Guoping Zhong1,2, Ying Wang3
1Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|March 13, 2024
概括
在巨细胞中激活Pregnane X受体 (PXR) 可以防止内毒性肝损伤. 这种激活通过STAT6通路将巨细胞偏向转移到抗炎M2类型,从而提供了一个新的治疗点.
科学领域:
- 肝病学和免疫学 肝病学和免疫学
- 疾病的分子机制.
背景情况:
- 内毒性导致急性肝损伤,死亡率高,涉及巨细胞两极分化.
- 孕妇X受体 (PXR) 是一种保护肝脏的核受体,但其在内毒性肝损伤中的作用尚不清楚.
研究的目的:
- 调查PXR激活在内毒性肝损伤期间巨细胞中的作用和机制.
主要方法:
- 检查了人类和小鼠巨细胞中的PXR表达.
- 在巨细胞中激活了PXR,并评估了它对肝损伤和两极分化的影响.
- 在小鼠中使用了巨细胞枯竭和PXR淘汰模型.
- 研究了PXR与STAT6信号的相互作用,在体外和体内.
主要成果:
- 激活PXR减轻了内毒性肝损伤,并促进了M2巨细胞的两极分化.
- 巨细胞的枯竭和PXR的淘汰削弱了PXR的保护作用.
- 在各种细胞类型中,PXR激活将M1偏向转移到M2偏向.
- PXR与STAT6相互作用,阻断两者取消了极化转移.
结论:
- 巨细胞PXR激活通过STAT6通路调节巨细胞极化,减轻内毒素诱导的肝损伤.
- 巨细胞中的PXR激活为内毒性肝损伤提供了潜在的治疗策略.
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