Choudhuri Subhadip, Garg Nisha Jain
Department of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, Texas, USA.
Institute for Human Infections and Immunity (IHII), University of Texas Medical Branch (UTMB), Galveston, Texas, USA.
Liver Int. 2025 Jun;45(6):e16245. doi: 10.1111/liv.16245.
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.
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.
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.
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.
肝细胞核因子4α（HNF4α）是胎儿及成年肝脏中肝细胞分化的主要调节因子，并在决定肝脏生理功能方面发挥转录作用。本综述的目的是阐述目前关于肝脏疾病发病机制多个方面中涉及HNF4α调节的分子机制的知识。
基于现有文献，本综述总结了HNF4α失调机制的当前知识状态，以及HNF4α活性在调节各种肝脏疾病从早期到晚期阶段中的作用。
HNF4α表达紊乱的患者患肝脏疾病（如病毒性肝炎、酒精性/非酒精性脂肪性肝病、肝细胞癌）以及血液系统疾病（如凝血病和出血性疾病）的风险更高。
HNF4α与核受体及靶基因的相互作用通过调节各种代谢途径促进肝脏疾病病理过程。HNF4α表达紊乱与肝脏疾病严重程度之间的强相关性表明，靶向HNF4α表达可为预防肝脏疾病病理过程和止血障碍提供潜在的治疗策略。
