通过FGF4抑制ERRγ-CYP2E1通路可以减轻与酒精有关的肝损伤
Luyao Wang1,2, Wenliya Dong1, Lei Fan1,2
1State Key Laboratory of Macromolecular Drugs and Large-scale Preparation, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Hepatology (Baltimore, Md.)
|February 26, 2025
概括
纤维细胞生长因子4 (FGF4) 在与酒精有关的肝病 (ALD) 中被上调,并通过降低ERRγ.恶化肝损伤. 准FGF4可能为ALD提供新的治疗方法.
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
- 生物化学 生物化学
背景情况:
- 酒精相关性肝病 (ALD) 是一个主要的健康问题,伤害机制不明.
- 纤维细胞生长因子4 (FGF4) 与肝病进展有关.
研究的目的:
- 调查FGF4在与酒精相关的肝病 (ALD) 病原发生中的作用.
主要方法:
- 对人类肝脏样本和ALD小鼠模型的分析.
- 研究了肝细胞特异Fgf4删除和Fgfr4淘汰的作用.
- 使用了ERRγ逆agonist GSK5182和CYP2E1抑制剂甲 (CMZ).
主要成果:
- 在ALD患者和小鼠模型中,FGF4mRNA和蛋白质水平升高,与疾病严重程度相关.
- 肝细胞特异性Fgf4缺失加剧了肝损伤,增加了氧化应激,炎症和亡.
- 被FGFR4介导的酸化和ERRγ被FGF4降解被确定为关键机制.
- 准FGFR4或下游途径缓解了酒精诱导的肝损伤.
结论:
- 在肝脏病理生理学中,FGF4通过FGFR4-ERRγ-CYP2E1通路作为应激反应调节剂.
- FGF4及其下游信号通路代表了ALD的潜在治疗点.
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