Reelin expression by hepatic stellate cells and ductular reaction in HCV related liver fibrosis

Reelin is a secreted extracellular glycoprotein that is thought to guide migrat- ing neurons during brain development and maturation cooperating with Disabled-1 (Dab1), an adaptor protein obligate effector of reelin signalling pathway (1). Reelin is also expressed in human liver by hepatic stellate cell(HSC)s that following liver injury become activated, migrating and fibrogenic cells (2). The cross-talk between HSCs and other cells such as those of ductular reaction (DR) is believed to rule liver fibrogenesis leading to cirrhosis (3). In order to better understand the role of ree- lin in human liver tissue with ongoing fibrosis, we aim to analyse the hepatic reelin expression and its relationship with the main histological determinants of the dis- ease activity and severity. Eighty-one liver biopsies of patients with chronic hepatitis C were studied. The expression of Reelin, Dab1, and HSC markers was investigated by immunohistochemistry and immunofluorescence. The Knodell histology activity index and DR score were evaluated. Activated HSC were frequently reelin positive and a statistical correlation was found between the number of reelin positive HSCs and Knodell’s stage (r= 0,3; p<0,05). Dab1 was expressed by cells of DR and the number of reelin positive HSCs correlated with DR score in mild/moderate fibrosis (r=0,4; p<0,05). Since reelin expression by HSCs correlates with increasing fibrosis and DR, whose cells in turn express Dab1, it might act as mediator in DR activation by HSCs. Further studies are needed to test reelin as useful biomarker for liver fibrosis assess- ment