BCP区突变的HBV转基因小鼠转录组学分析  

Transcriptomic analysis of the BCP-mutated HBV transgenic mice

作　　者：朱琴 苏瑜 杨咏玉 谢黎 陈鸿 杨乐 卜凡 邓强 吴健 蒋炜 ZHU Qin;SU Yu;YANG Yongyu;XIE Li;CHEN Hong;YANG Le;BU Fan;DENG Qiang;WU Jian;JIANG Wei(Department of Gastroenterology and Hepatology,Zhongshan Hospital of Fudan University,Shanghai 200032,China;Department of Medical Microbiology and Parasitology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China;Shanghai Institute of Liver Diseases,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院消化内科,上海200032 [2]复旦大学基础医学院病原生物学系,教育部/卫健委医学分子病毒学重点实验室,上海200032 [3]上海市肝病研究所,上海200032

出　　处：《微生物与感染》2024年第5期257-266,共10页Journal of Microbes and Infections

基　　金：国家自然科学基金项目(82370622)。

摘　　要：乙型肝炎病毒(hepatitis B virus,HBV)慢性感染可引发肝硬化、肝细胞癌等严重肝病,对全球健康造成重大威胁。本研究利用基本核心启动子(basic core promoter,BCP)突变的HBV转基因小鼠模型,评估其病毒学特征和肝损伤情况。本研究通过肝组织天狼猩红染色和全基因转录组学分析,发现12周龄的BCP区突变HBV转基因小鼠表现出HBV DNA高复制水平和自发性肝纤维化。差异基因分析显示,HBV-Tg组有729个基因上调,325个基因下调。这些差异表达基因主要富集于细胞外基质、PPAR通路以及细胞色素P450通路等。蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络互作揭示,关键基因涉及胶原合成、炎症反应以及细胞周期和死亡等。该模型小鼠的病理变化与慢性肝病进展一致,可为HBV感染相关肝病的机制研究提供可靠且有效的模型。Chronic infection with the hepatitis B virus(HBV)is a significant contributor to severe liver diseases,including cirrhosis and hepatocellular carcinoma,thereby posing a substantial global health concern.This investigation employed an HBV transgenic mouse model harboring mutations in the basal core promoter(BCP)region to assess the model’s virological characteristics and hepatic damage.The extent of liver fibrosis was determined using sirius red staining of liver tissue.Furthermore,whole-genome transcriptomic analysis of liver tissue was conducted.The study revealed that 12-week-old HBV transgenic mice with BCP region mutations exhibited increased HBV DNA replication levels and spontaneous liver fibrosis.Differential gene expression analysis identified 729 upregulated and 325 down-regulated genes within the HBV-Tg cohort,which predominantly associated with the extracellular matrix,peroxisome proliferator-activated receptor(PPAR)pathway,and cytochrome P450 pathway.Protein-protein interaction(PPI)network analysis indicated that pivotal genes were implicated in collagen synthesis,inflammatory response,cell cycle regulation,and apoptosis.The pathological alterations observed in this murine model align with the progression of chronic liver disease,thus providing a robust and effective model for elucidating the mechanisms underlying HBV infection-related hepatic pathology.

关 键 词：乙型肝炎病毒 慢性乙型病毒性肝炎 转录组学 

分 类 号：R575[医药卫生—消化系统]