Roles and potential mechanisms of hepatic stellate cells activation mediated by epigenetics through insulin like growth factor 1 and receptor: A review

Hepatic stellate cells (HSCs) activation is the central event of liver fibrosis caused by various factors and targeting HSCs has become a major strategy for the treatment of liver fibrosis. Insulin like growth factor 1 (IGF1) and IGF1 receptor (IGF1R) are mainly expressed in the liver tissues and play critical roles in the liver function and HSCs activation. The present review firstly summarized the regulation and mechanisms of HSCs activation, then illustrated the potential roles of IGF1/IGF1R as target in HSCs apoptosis, aHSCs inactivation and senescence. Considering the significance of IGF1/IGF1R in HSCs activation and the epigenetic modifications, as well as the relationship of HSCs activation and epigenetic modifications, we further collated the effects on HSCs activation by IGF1/IGF1R interactions with epigenetics modifications, including the DNA methylation, histone modification and non-coding RNAs, forecasting the role of epigenetic modifications in HSCs activation and liver fibrosis. Finally, in addition to the mechanism, we summarized the current and potential therapies targeting IGF1/IGF1R or epigenetic modifications, along with the challenges involved, and proposed more epigenetic modifications in liver-specific functions should be further studied, such as palmitoylation and succinylation regulated by IGF1/IGF1R.