Reversibility and heritability of liver fibrosis:Implications for research and therapy  

作　　者：Hussein M Atta 

机构地区：[1]Department of Surgery,Faculty of Medicine,Minia University,El-Minia 61519,Egypt

出　　处：《World Journal of Gastroenterology》2015年第17期5138-5148,共11页世界胃肠病学杂志（英文版）

基　　金：Egyptian Science and Technology Development Fund under Project 1550

摘　　要：Liver fibrosis continues to be a major health problem worldwide due to lack of effective therapy.If the etiology cannot be eliminated,liver fibrosis progresses to cirrhosis and eventually to liver failure or malignancy;both are associated with a fatal outcome.Liver transplantation,the only curative therapy,is still mostly unavailable.Liver fibrosis was shown to be a reversible process;however,complete reversibility remains debatable.Recently,the molecular markers of liver fibrosis were shown to be transmitted across generations.Epigenetic mechanisms including DNA methylation,histone posttranslational modifications and noncoding RNA have emerged as major determinants of gene expression during liver fibrogenesis and carcinogenesis.Furthermore,epigenetic mechanisms have been shown to be transmitted through mitosis and meiosis to daughter cells and subsequent generations.However,the exact epigenetic regulation of complete liver fibrosis resolution and inheritance has not been fully elucidated.This communication will highlight the recent advances in the search for delineating the mechanisms governing resolution of liver fibrosis and the potential for multigenerational and transgenerational transmission of fibrosis markers.The fact that epigenetic changes,unlike genetic mutations,are reversible and can be modulated pharmacologically underscores the unique opportunity to develop effective therapy to completely reverse liver fibrosis,to prevent the development of malignancy and to regulate heritability of fibrosis phenotype.Liver fibrosis continues to be a major health problem worldwide due to lack of effective therapy.If the etiology cannot be eliminated,liver fibrosis progresses to cirrhosis and eventually to liver failure or malignancy;both are associated with a fatal outcome.Liver transplantation,the only curative therapy,is still mostly unavailable.Liver fibrosis was shown to be a reversible process;however,complete reversibility remains debatable.Recently,the molecular markers of liver fibrosis were shown to be transmitted across generations.Epigenetic mechanisms including DNA methylation,histone posttranslational modifications and noncoding RNA have emerged as major determinants of gene expression during liver fibrogenesis and carcinogenesis.Furthermore,epigenetic mechanisms have been shown to be transmitted through mitosis and meiosis to daughter cells and subsequent generations.However,the exact epigenetic regulation of complete liver fibrosis resolution and inheritance has not been fully elucidated.This communication will highlight the recent advances in the search for delineating the mechanisms governing resolution of liver fibrosis and the potential for multigenerational and transgenerational transmission of fibrosis markers.The fact that epigenetic changes,unlike genetic mutations,are reversible and can be modulated pharmacologically underscores the unique opportunity to develop effective therapy to completely reverse liver fibrosis,to prevent the development of malignancy and to regulate heritability of fibrosis phenotype.

关 键 词：EPIGENETICS Epimutations Inheritance LIVERCIRRHOSIS Hepatic stellate cells HISTONE modification DNA methylation MicroRNA Long noncoding RNA Transcription regulation 

分 类 号：R575.2[医药卫生—消化系统]