Epigenetic modification in liver fibrosis:Promising therapeutic direction with significant challenges ahead

作     者：Runping Liu Yajing Li Qi Zheng Mingning Ding Huiping Zhou Xiaojiaoyang Li Runping Liu;Yajing Li;Qi Zheng;Mingning Ding;Huiping Zhou;Xiaojiaoyang Li

作者机构：School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing 102400China School of Life SciencesBeijing University of Chinese MedicineBeijing 102400China Department of Microbiology and ImmunologyVirginia Commonwealth UniversityRichmondVA 22460USA 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2024年第14卷第3期

页      面：1009-1029页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 10[医学] 

基　　金：supported by the National Key Research and Development Program on Modernization of Traditional Chinese Medicine(Grant No.2022YFC3502104,China) supports from VA Merit Award 5 I01 BX005730 National Institutes of Health Grant R01 R01DK-057543 to Huiping Zhou(USA) National High-Level Talents Special Support Program to Xiaojiaoyang Li(China) Fundamental Research Funds for the Central Universities(Grant No.2023-JYBJBZD-046 to Xiaojiaoyang Li,China)。 

主　　题：Liver fibrosis Epigenetics regulation DNA methylation Histone acetylation Histone methylation mRNA methylation Non-coding RNA Drug development 

摘      要：Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver failure.It’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver diseases.However,current treatment options are limited,highlighting the urgent need for the development of new therapies.As a reversible regulatory mechanism,epigenetic modification is implicated in many biological processes,including liver fibrosis.Exploring the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases,although the current evidence is still controversial.This review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications,including DNA methylation,histone modification,and RNA modification,in liver fibrotic diseases.The potential cooperation of different epigenetic modifications in promoting fibrogenesis was also highlighted.Finally,available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were discussed.In summary,elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.