Author/Authors :
Thoeni, Cornelia Institute of Pathology - University Hospital Heidelberg, Germany , Waldherr, Ruediger Institute of Pathology - University Hospital Heidelberg, Germany , Scheuerer, Jutta Institute of Pathology - University Hospital Heidelberg, Germany , Schmitteckert, Stefanie Department of Human Molecular Genetics - Institute of Human Genetics - University Heidelberg, Germany , Roeth, Ralph Department of Human Molecular Genetics - Institute of Human Genetics - University Heidelberg, Germany , Niesler, Beate Department of Human Molecular Genetics - Institute of Human Genetics - University Heidelberg, Germany , Cutz, Ernest Division of Pathology - Department of Paediatric Laboratory Medicine (DPLM) - 1e Hospital for Sick Children - University of Toronto, Canada , Flechtenmacher, Christa Institute of Pathology - University Hospital Heidelberg, Germany , Goeppert, Benjamin Institute of Pathology - University Hospital Heidelberg, Germany , Schirmacher, Peter Institute of Pathology - University Hospital Heidelberg, Germany , Lasitschka, Felix Institute of Pathology - University Hospital Heidelberg, Germany
Abstract :
ATP-binding cassette (ABC) transporters are the members of the efflux pumps that are responsible for the removal of cytotoxic substances by active transport. ABCB11, the bile salt efflux pump of hepatocytes, coordinates cellular excretion of numerous conjugated bile salts into the bile canaliculi, whereas ABCB4 acts as an ATP-dependent floppase translocating phosphatidylcholine from the inner to the outer leaflet of the bile canalicular membrane. Loss of functional ABCB11 and ABCB4 proteins causes early-onset refractory cholestasis or cholangiopathy. In this study, we investigated the expression and localization pattern of ABCB11 and ABCB4 using immunohistochemistry and RNA profiling in liver samples from patients with different types and stages of chronic cholestatic liver disease, with emphasis on primary sclerosing cholangitis (PSC), compared to a variety of cholestatic and noncholestatic hepatopathies. Therefore, ABCB11 and ABCB4 expressions were investigated on formalin-fixed and paraffin-embedded (FFPE) material in a patient cohort of total 43 patients with or without cholestatic liver diseases, on protein level using immunohistochemistry and on RNA level using nanoString technology. Intriguingly, our results demonstrated increased expression of ABCB11 and ABCB4 on protein as well as RNA level in PSC, and the expression pattern correlated with disease progression. We concluded from our study that patients with PSC demonstrate altered expression levels and pattern of ABCB11 and ABCB4 which correlated with disease progression; thereby, ABCB11 and ABCB4 analysis may be a useful tool for assessment of disease stages in PSC.
Keywords :
Expression Analysis , ATP-Binding Cassette Transporters ABCB11 , ABCB4 , Primary Sclerosing Cholangitis
