Institute for Liver Diseases of Anhui Medical University, Hefei 230032, Anhui Province, China.
Cell Signal. 2013 Sep;25(9):1837-44. doi: 10.1016/j.cellsig.2013.05.017. Epub 2013 May 22.
Epigenetics refers to the study of heritable changes in the pattern of gene expression that is controlled by a mechanism specifically not due to changes the primary DNA sequence. Well-known epigenetic mechanisms include DNA methylation, post-translational histone modifications and RNA-based mechanisms including those controlled by small non-coding RNAs (miRNAs). Recent studies have shown that epigenetic modifications orchestrate the hepatic stellate cell (HSC) activation and liver fibrosis. In this review we focus on the aberrant methylation of CpG island promoters of select genes is the prominent epigenetic mechanism to effectively silence gene transcription facilitating HSC activation and liver fibrosis. Furthermore, we also discuss epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation and the interaction of DNA methylation with miRNAs involved in the regulation of HSC activation and liver fibrosis. Recent advances in epigenetics alterations in the pathogenesis of liver fibrosis and their possible use as new therapeutic targets and biomarkers.
表观遗传学是指研究基因表达模式的可遗传变化,这种变化受一种特定的机制控制,而不是由于主要 DNA 序列的变化。众所周知的表观遗传机制包括 DNA 甲基化、组蛋白翻译后修饰以及基于 RNA 的机制,包括由小非编码 RNA(miRNA)控制的机制。最近的研究表明,表观遗传修饰协调肝星状细胞(HSC)的激活和肝纤维化。在这篇综述中,我们重点讨论了特定基因的 CpG 岛启动子的异常甲基化是一种显著的表观遗传机制,可有效地沉默基因转录,促进 HSC 的激活和肝纤维化。此外,我们还讨论了肿瘤抑制 miRNA 基因启动子 DNA 甲基化的表观遗传失调以及 DNA 甲基化与 miRNA 之间的相互作用,这些 miRNA 参与了 HSC 激活和肝纤维化的调控。最近在肝纤维化发病机制中的表观遗传学改变方面取得了进展,它们可能作为新的治疗靶点和生物标志物得到应用。