Epigenetic regulation during hepatic stellate cell activation

Excerpt

Hepatic stellate cells (HSC) have recently been identified as liver-resident mesenchymal stem cells and are thought to contribute to liver repair and fibrogenesis [1]. Quiescent HSC are located in the space of Disse and store vitamin A in characteristic lipid droplets. During their activation HSC lose their vitamin A stores and adopt a myofibroblast-like phenotype. This activation of HSC is necessary to enable hepatic differentiation and is accompanied by changes in the expression of many genes such as extracellular matrix protein encoding genes [2]. Some of these genes like Notch1 and Notch3 are regulated by epigenetic mechanisms. Their expression depends on the promoter DNA methylation and is changed during HSC activation [3]. The aim of the present study is a comprehensive analysis of DNA methylation alterations during HSC activation at a global and gene-specific level to elucidate their impact on hepatic stellate cell activation and to identify basic mechanisms of epigenetic control in adult stem cells during differentiation. …