Interplay between YAP/TAZ and metabolic dysfunction-associated steatotic liver disease progression

IF 6.9 3区 医学 Q1 CHEMISTRY, MEDICINAL
Na Young Lee, Myeung Gi Choi, Eui Jin Lee, Ja Hyun Koo
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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.

Abstract Image

YAP/TAZ与代谢功能障碍相关脂肪性肝病进展之间的相互作用
代谢功能障碍相关性脂肪性肝病(MASLD)正成为日益紧迫的全球健康挑战,死亡率呈上升趋势。每年有 200 万人死于肝硬化和肝癌。是相关蛋白(YAP)和具有 PDZ 结合基调的转录辅激活因子(TAZ)是 Hippo 信号通路的关键效应因子,对肝脏组织的稳态和疾病进展起着至关重要的调节作用。初步研究表明,在健康肝脏中,YAP 的表达通常仅限于胆管细胞,但在慢性肝病期间,YAP/TAZ 在其他肝细胞中也被观察到活化。疾病驱动的 YAP/TAZ 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。在本研究中,我们重点研究了 YAP/TAZ 在 MASLD 中的复杂作用,并探讨了 YAP/TAZ 的失调如何驱动脂肪变性、炎症、纤维化和肝硬化。最后,我们讨论了YAP/TAZ在肝细胞、肝星状细胞、肝巨噬细胞和胆道上皮细胞等不同类型肝细胞中的细胞特异性功能,突出了YAP/TAZ对肝脏生理和病理的多方面影响。
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来源期刊
CiteScore
13.40
自引率
9.00%
发文量
48
审稿时长
3.3 months
期刊介绍: Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.
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