Expression of Cyclin E1 and Cdk2 in Hepatic Stellate Cells is critical for initiation and progression of liver fibrosis in mice

Background and aims Liver fibrogenesis is a wound healing process characterized by the accumulation of extracellular collagen produced by Hepatic Stellate Cells (HSCs). Initiation of liver fibrosis involves cell cycle re-entry and thus activation and proliferation of normally quiescent HSCs. It is believed that the cyclin-dependent kinase 2 (Cdk2) together with its regulatory subunit Cyclin E controls cell cycle re-entry. We have recently shown that constitutive ablation of Cyclin E1 (CcnE1) in mice inhibited liver fibrogenesis. However, the effector cells of CcnE1 during fibrogenesis are not known so far and it has also not been clarified yet, whether the pro-fibrotic effect of CcnE1 depends on the kinase activity of Cdk2. Thus the aim of the present study was to evaluate the contribution of CcnE1 and Cdk2 specifically in HSCs for liver fibrogenesis.