Mann Derek A, Mann Jelena
Liver Research Group, School of Clinical Medical Sciences, University of Newcastle, Newcastle upon Tyne, UK.
J Gastroenterol Hepatol. 2008 Mar;23 Suppl 1:S108-11. doi: 10.1111/j.1440-1746.2007.05295.x.
Activation of hepatic stellate cells (HSC) to a myofibroblast-like phenotype is the pivotal event in liver fibrosis. In uninjured liver, HSC are quiescent and non-dividing, but upon liver injury these cells undergo a dramatic change in phenotype which generates activated myofibroblast-like HSC. The change in phenotype is underpinned by a global change in gene expression with hundreds of genes being up- or downregulated. Molecular events that orchestrate changes in gene expression take place at the level of chromatin packaging which is altered through three main processes: histone modifications, DNA methylation, and silencing by non-coding RNAs. The present review focuses on the epigenetic regulation of HSC activation.
肝星状细胞(HSC)激活为肌成纤维细胞样表型是肝纤维化的关键事件。在未受损的肝脏中,HSC处于静止且不分裂状态,但在肝脏损伤时,这些细胞会发生显著的表型变化,从而产生活化的肌成纤维细胞样HSC。表型变化的基础是基因表达的全局性改变,数百个基因被上调或下调。协调基因表达变化的分子事件发生在染色质包装水平,染色质包装通过三个主要过程发生改变:组蛋白修饰、DNA甲基化和非编码RNA介导的沉默。本综述聚焦于HSC激活的表观遗传调控。