title: Reelin expression in human liver of patients with chronic hepatitis C infection.
abstract: Reelin is a secreted extracellular glycoprotein that plays a critical role during brain development. Several studies have described Reelin expression in hepatic stellate cells of the human liver. In order to investigate the possible role of Reelin in the process of hepatic fibrogenesis, in this study we investigated Reelin expression in the liver tissue of patients infected with the Hepatitis C Virus (HCV). On this basis, Reelin expression was analysed by immunohistochemistry during liver biopsies of 81 patients with HCV-related chronic hepatitis. A Knodell score was used to stage liver fibrosis. Hepatic stellate cells/myofibroblast immunohistochemical markers (CRBP-1, alpha-SMA) were also evaluated. As further confirmed by co-localization experiments (Reelin +CRBP-1), Reelin protein was expressed by hepatic stellate cells/myofibroblasts, and a significant positive correlation was found between Reelin expression and the stage of liver fibrosis (P=0.002). Moreover, Reelin correlated with CRBP-1 positive cells (P=0.002), but not with alpha-SMA, suggesting that Reelin should not be regarded as a marker of hepatic stellate cells/myofibroblasts differentiation but rather as a functional protein expressed during some phases of liver fibrosis. Furthermore, Disabled-1 (Dab1), a Reelin adaptor protein, was expressed in cells of ductular reaction suggesting a paracrine role for Reelin with regards these elements. In conclusion, Reelin was expressed by human hepatic stellate cells/myofibroblasts and the number of these cells increased significantly in the lobule as the liver fibrosis progressed, suggesting a role for Reelin in the activation of hepatic stellate cells/myofibroblasts during liver injury. Reelin may potentially be incorporated into liver injury evaluations in combination with other histological data.
authors.affiliation: Campus Bio-Medico University, Laboratory of Microscopic and Ultrastructural Anatomy. s.carotti@unicampus.it.
authors.forename: Simone
authors.initials: S
authors.lastname: Carotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Perrone
authors.forename: Michelina
authors.initials: M
authors.lastname: Amato
authors.forename: Umberto
authors.initials: U
authors.lastname: Vespasiani Gentilucci
authors.forename: Daniela
authors.initials: D
authors.lastname: Righi
authors.forename: Maria
authors.initials: M
authors.lastname: Francesconi
authors.forename: Claudio
authors.initials: C
authors.lastname: Pellegrini
authors.forename: Francesca
authors.initials: F
authors.lastname: Zalfa
authors.forename: Maria
authors.initials: M
authors.lastname: Zingariello
authors.forename: Antonio
authors.initials: A
authors.lastname: Picardi
authors.forename: Andrea
authors.initials: A
authors.lastname: Onetti Muda
authors.forename: Sergio
authors.initials: S
authors.lastname: Morini
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005260:Female; D005786:Gene Expression Regulation; D016174:Hepacivirus; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000096:biosynthesis*
chemical_list: D015415:Biomarkers; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases