肝细胞核因子4 α：肝脏疾病病理和止血障碍的关键调节因子

IF 6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver International Pub Date : 2025-05-19 DOI:10.1111/liv.16245

Subhadip Choudhuri, Nisha Jain Garg

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引用次数: 0

摘要

目的肝细胞核因子4α (HNF4α)是胎儿和成人肝脏中肝细胞分化的主要调控因子，其转录作用决定肝脏的生理功能。本综述的目的是解决HNF4α在肝脏疾病发病机制的多个方面参与调控的分子机制的现有知识。方法在现有文献的基础上，综述了HNF4α表达异常的机制，以及HNF4α活性异常在各种肝脏疾病的早期至晚期中的作用。结果HNF4α表达紊乱的患者发生病毒性肝炎、酒精性/非酒精性脂肪肝、肝细胞癌等肝脏疾病和凝血功能障碍、出血性疾病等血液系统疾病的风险较高。HNF4α与核受体和靶基因的相互作用通过调节多种代谢途径促进肝脏疾病的病理。紊乱的HNF4α表达与肝脏疾病严重程度之间的强相关性表明，靶向HNF4α表达可以为预防肝脏疾病病理和止血障碍提供潜在的治疗策略。

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Hepatocyte Nuclear Factor 4 Alpha: A Key Regulator of Liver Disease Pathology and Haemostatic Disorders

Objective

Hepatocyte nuclear factor 4 alpha (HNF4α) is a master regulator of hepatocyte differentiation in fetal and adult liver and exerts its transcriptional role in determining physiological functions of the liver. The objective of this review is to address the current knowledge of molecular mechanisms involved in HNF4α regulation in multiple aspects of liver disease pathogenesis.

Methods

Based on available literature, this review summarises the current state of knowledge onthe mechanism of HNF4α dysregulation, and the role of HNF4α activity inregulating early to advanced stages of various liver diseases.

Results

Patients with deranged HNF4α expression are at higher risk for the development of liver diseases such as viral hepatitis, alcoholic/nonalcoholic fatty liver disease, hepatocellular carcinoma, and haematological disorders such as coagulopathy and bleeding disorders.

Discussion

HNF4α interactions with nuclear receptors and target genes promote liver disease pathology by regulating various metabolic pathways. The strong correlation between deranged HNF4α expression and the severity of liver diseases suggests that targeting HNF4α expression can offer potential therapeutic strategy in the prevention of liver disease pathology and haemostatic disorders.

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来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.