The Sugar-Coated Truth of Alcohol-Associated Liver Disease: Galectins as Multifaceted Regulators of Alcohol-Induced Liver Injury.

IF 3.6 2区 医学 Q1 PATHOLOGY
Doug Terry, Brian S Robinson
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引用次数: 0

Abstract

Alcohol-associated diver disease is a major driver of end-stage liver diseases globally. Alcohol functions as a hepatotoxin by overwhelming cell stress response pathways and deregulating hepatocellular protein, amino acid, and lipid metabolism. In addition, alcohol alters innate and adaptive inflammatory immune responses and acts on extrahepatic organs to flood the liver with pro-inflammatory stimuli. Here we examine how galectins, a class of highly conserved carbohydrate-binding proteins, regulate liver homeostasis and pathology. Next, we define how galectins affect key pathways that drive alcohol-induced liver disease, including hepatocyte cell biology (eg, altered lipid metabolism, endoplasmic reticulum and lysosomal stress, mitochondrial dysfunction), innate and immune response, intestinal dysfunction, and liver fibrosis. We then document the roles of galectins in the setting of alcohol-associated liver disease. Finally, we discuss galectins as theragnostic markers and therapeutic targets for alcohol-associated liver disease and address key open questions in the field.

酒精相关肝病的糖衣真相:半乳糖凝集素作为酒精性肝损伤的多方面调节因子
酒精相关性肝病是全球终末期肝病的主要驱动因素。酒精作为一种肝毒素,通过压倒细胞应激反应途径和解除肝细胞蛋白质、氨基酸和脂质代谢的调节而发挥作用。此外,酒精改变先天和适应性炎症免疫反应,并作用于肝外器官,使肝脏充满促炎刺激。在这里,我们研究了凝集素,一类高度保守的碳水化合物结合蛋白,如何调节肝脏稳态和病理。接下来,我们定义了半乳糖凝集素如何影响驱动酒精诱导的肝脏疾病的关键途径,包括肝细胞细胞生物学(例如,脂质代谢改变、内质网和溶酶体应激、线粒体功能障碍)、先天和免疫反应、肠道功能障碍和肝纤维化。然后我们继续记录凝集素在酒精相关肝脏疾病中的作用。最后,我们讨论了凝集素作为酒精相关肝病的诊断标志物和治疗靶点,并解决了该领域的关键开放性问题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
11.40
自引率
0.00%
发文量
178
审稿时长
30 days
期刊介绍: The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.
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