Shojaie Layla, Iorga Andrea, Dara Lily
Division of Gastrointestinal & Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Research Center for Liver Disease, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Int J Mol Sci. 2020 Dec 18;21(24):9682. doi: 10.3390/ijms21249682.
Regulated cell death (RCD) is pivotal in directing the severity and outcome of liver injury. Hepatocyte cell death is a critical event in the progression of liver disease due to resultant inflammation leading to fibrosis. Apoptosis, necrosis, necroptosis, autophagy, and recently, pyroptosis and ferroptosis, have all been investigated in the pathogenesis of various liver diseases. These cell death subroutines display distinct features, while sharing many similar characteristics with considerable overlap and crosstalk. Multiple types of cell death modes can likely coexist, and the death of different liver cell populations may contribute to liver injury in each type of disease. This review addresses the known signaling cascades in each cell death pathway and its implications in liver disease. In this review, we describe the common findings in each disease model, as well as the controversies and the limitations of current data with a particular focus on cell death-related research in humans and in rodent models of alcoholic liver disease, non-alcoholic fatty liver disease and steatohepatitis (NASH/NAFLD), acetaminophen (APAP)-induced hepatotoxicity, autoimmune hepatitis, cholestatic liver disease, and viral hepatitis.
程序性细胞死亡（RCD）在决定肝损伤的严重程度和结局方面起着关键作用。肝细胞死亡是肝病进展中的一个关键事件，因为由此产生的炎症会导致纤维化。凋亡、坏死、坏死性凋亡、自噬，以及最近发现的焦亡和铁死亡，都已在各种肝病的发病机制中得到研究。这些细胞死亡子程序表现出不同的特征，同时也有许多相似之处，存在大量重叠和相互作用。多种类型的细胞死亡模式可能同时存在，不同肝细胞群体的死亡可能在每种疾病类型中导致肝损伤。本综述阐述了每种细胞死亡途径中已知的信号级联及其在肝病中的意义。在本综述中，我们描述了每种疾病模型中的常见发现，以及当前数据存在的争议和局限性，特别关注人类以及酒精性肝病、非酒精性脂肪性肝病和脂肪性肝炎（NASH/NAFLD）、对乙酰氨基酚（APAP）诱导的肝毒性、自身免疫性肝炎、胆汁淤积性肝病和病毒性肝炎的啮齿动物模型中与细胞死亡相关的研究。
