抑制Wnt信号通过破坏炎症轴来减少胆固醇损伤
Mary Ayers1, Karis Kosar2, Yuhua Xue2
1Department of Pediatric Gastroenterology, Hepatology, and Nutrition, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
Cellular and molecular gastroenterology and hepatology
|August 14, 2023
概括
抑制Wnt信号传递通过抑制胆细胞激活和核因子kappa B信号传递来减少肝损伤和胆质炎症. 这种方法为胆道疾病提供了潜在的治疗策略.
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
- 信号通道的信号通道
背景情况:
- 由β-catenin介导的Wnt信号通过抑制Farnesoid X受体 (FXR) 影响胆酸稳态.
- 胆固醇症涉及失调的胆酸代谢,可能导致肝损伤和纤维化.
- 针对Wnt信号和FXR激活是胆固醇性肝病的潜在治疗策略.
研究的目的:
- 在胆固醇的小鼠模型中,研究同时抑制β-catenin信号传递和FXR激活的治疗潜力.
- 评估Wnt信号抑制对胆酸合成,肝损伤和胆管纤维化的影响.
主要方法:
- 在野生型小鼠中,通过胆道绑定 (BDL) 诱导胆固醇.
- 治疗小鼠的方法是使用FXR激活剂 (obeticholic acid, tropifexor, GW-4064) 或Wnt抑制剂 (Wnt-C59).
- 肝损伤,基因表达和胆血管细胞激活在治疗5天和12天后进行了评估.
主要成果:
- FXR激动剂加剧了BDL诱导的肝损伤,而Wnt-C59没有.
- 在12天后,Wnt-C59治疗减少了BDL小鼠的肝脏梗塞和炎症细胞.
- 抑制Wnt信号传递抑制了核因子kappa B (NF-κB) 信号传递和胆血管细胞激活,促进了静止状态.
结论:
- 抑制Wnt信号抑制通过抑制胆细胞激活来减少胆固醇性肝损伤.
- 对NF-κB依赖性炎症轴的破坏有助于Wnt抑制的保护作用.
- 准Wnt信号提供了一个有前途的治疗途径,用于胆固醇性肝脏疾病.
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