自噬
上皮-间质转换
河马信号通路
诺比林
纤维化
癌症研究
炎症
肝细胞
化学
细胞生物学
医学
生物
下调和上调
免疫学
信号转导
病理
细胞凋亡
生物化学
抗氧化剂
类黄酮
基因
体外
作者
Yuting Hao,Dongliang Feng,Hongyan Ye,Tiantian Zhang
标识
DOI:10.1002/mnfr.202300529
摘要
Scope The current researches indicated that the epithelial–mesenchymal transition (EMT) of hepatocytes plays a crucial role in the development of liver fibrosis. To date, there is a paucity of literature regarding the impact of nobiletin (NOB) on liver fibrosis. This study investigates the inhibitory effect of NOB on EMT in hepatocytes during the progression of liver fibrosis and its underlying mechanism. Methods and results The findings demonstrated that NOB significantly suppresses liver fibrosis in carbon tetrachloride (CCl 4 )‐induced mice by reducing inflammation and fiber deposition in the liver. Moreover, NOB mitigates EMT in hepatocytes, concurrently alleviating inflammatory status and reducing the production of reactive oxygen species (ROS) generation. The comprehensive investigation reveals that the hepatoprotective effect of NOB in liver fibrosis is attributed to autophagy activation, as evidenced by a significant increase in LC3 II expression and p62 degradation upon NOB treatment. Additionally, NOB activates the Hippo/YAP pathway by downregulating YAP and its downstream targets in liver fibrosis, which is regulated by autophagy based on experiments with chloroquine (CQ), 3‐methyladenine (3‐MA), and siYAP intervention. Conclusion Therefore, this study provides evidences that NOB can protect hepatocytes from undergoing EMT during liver fibrosis by inducing autophagy and subsequently modulating the Hippo/YAP pathway.
科研通智能强力驱动
Strongly Powered by AbleSci AI