Targeting liver fibrosis by siRNA-mediated inhibition of Cyclin E1 in mice

Background & Aims: Initiation and progression of liver fibrosis requires proliferation and activation of resting hepatic stellate cells (HSC). Cyclin E1 is the regulatory subunit of the Cyclin-dependent Kinase 2 (Cdk2) and a key factor for initiation of cell cycle re-activation. We have recently shown that genetic inactivation of Cyclin E1 prevents activation, proliferation and survival of HSC and protects from liver fibrogenesis. The aim of the present study is to translate these findings into pre-clinical application by inhibiting Cyclin E1 using a siRNA based approach. Methods: The efficiency of several siRNA…