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Reelin expression in human liver of patients with chronic hepatitis C infection

Simone Carotti, Giuseppe Perrone, Michelina Amato, Umberto Vespasiani Gentilucci, Daniela Righi, Maria Francesconi, Claudio Pellegrini, Francesca Zalfa, Maria Zingariello, Antonio Picardi, Andrea Onetti Muda, Sergio Morini
  • Simone Carotti
    Campus Bio-Medico University, Laboratory of Microscopic and Ultrastructural Anatomy, Italy
  • Giuseppe Perrone
    Campus Bio-Medico University, Laboratory of Microscopic and Ultrastructural Anatomy, Italy | g.perrone@unicampus.it
  • Michelina Amato
    Campus Bio-Medico University, Department of Pathology, Italy
  • Umberto Vespasiani Gentilucci
    Campus Bio-Medico University, Internal Medicine and Hepatology Unit, Italy
  • Daniela Righi
    Campus Bio-Medico University, Department of Pathology, Italy
  • Maria Francesconi
    Campus Bio-Medico University, Laboratory of Microscopic and Ultrastructural Anatomy, Italy
  • Claudio Pellegrini
    Campus Bio-Medico University, Department of Pathology, Italy
  • Francesca Zalfa
    Campus Bio-Medico University, Laboratory of Microscopic and Ultrastructural Anatomy, Italy
  • Maria Zingariello
    Campus Bio-Medico University, Laboratory of Microscopic and Ultrastructural Anatomy, Italy
  • Antonio Picardi
    Campus Bio-Medico University, Internal Medicine and Hepatology Unit, Italy
  • Andrea Onetti Muda
    Campus Bio-Medico University, Department of Pathology, Italy
  • Sergio Morini
    Campus Bio-Medico University, Laboratory of Microscopic and Ultrastructural Anatomy, Italy

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.

Keywords

Reelin; liver fibrosis; HCV; hepatic stellate cells; Dab1.

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Submitted: 2016-10-27 13:18:19
Published: 2017-03-17 15:28:58
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Copyright (c) 2017 Simone Carotti, Giuseppe Perrone, Michelina Amato, Umberto Vespasiani Gentilucci, Daniela Righi, Maria Francesconi, Claudio Pellegrini, Francesca Zalfa, Maria Zingariello, Antonio Picardi, Andrea Onetti Muda, Sergio Morini

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