PDF(Pubmed)
Abstract：
Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming an increasingly pressing global health challenge, with increasing mortality rates showing an upward trend. Two million deaths occur annually from cirrhosis and liver cancer together each year. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), key effectors of the Hippo signaling pathway, critically regulate tissue homeostasis and disease progression in the liver. While initial studies have shown that YAP expression is normally restricted to cholangiocytes in healthy livers, the activation of YAP/TAZ is observed in other hepatic cells during chronic liver disease. The disease-driven dysregulation of YAP/TAZ appears to be a critical element in the MASLD progression, contributing to hepatocyte dysfunction, inflammation, and fibrosis. In this study, we focused on the complex roles of YAP/TAZ in MASLD and explored how the YAP/TAZ dysregulation of YAP/TAZ drives steatosis, inflammation, fibrosis, and cirrhosis. Finally, the cell-type-specific functions of YAP/TAZ in different types of hepatic cells, such as hepatocytes, hepatic stellate cells, hepatic macrophages, and biliary epithelial cells are discussed, highlighting the multifaceted impact of YAP/TAZ on liver physiology and pathology.
摘要：
代谢功能障碍相关的脂肪变性肝病（MASLD）正在成为一个日益紧迫的全球健康挑战，死亡率呈上升趋势。每年有两百万人死于肝硬化和肝癌。Yes相关蛋白（YAP）和具有PDZ结合基序（TAZ）的转录共激活因子，Hippo信号通路的关键效应子，关键调节组织稳态和肝脏疾病进展。虽然最初的研究表明，YAP的表达通常仅限于健康肝脏中的胆管细胞，在慢性肝病期间，在其他肝细胞中观察到YAP/TAZ的激活。YAP/TAZ的疾病驱动失调似乎是MASLD进展的关键因素，导致肝细胞功能障碍，炎症,和纤维化。在这项研究中,我们专注于YAP/TAZ在MASLD中的复杂作用，并探讨了YAP/TAZ的YAP/TAZ失调如何驱动脂肪变性，炎症,纤维化，和肝硬化。最后,YAP/TAZ在不同类型肝细胞中的细胞类型特异性功能，如肝细胞，肝星状细胞，肝巨噬细胞,讨论了胆管上皮细胞，强调YAP/TAZ对肝脏生理和病理的多方面影响。
