Expression Analysis of ATP-Binding Cassette Transporters ABCB11 and ABCB4 in Primary Sclerosing Cholangitis and Variety of Pediatric and Adult Cholestatic and Noncholestatic Liver Diseases
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, w...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Canadian Journal of Gastroenterology and Hepatology |
| Online Access: | http://dx.doi.org/10.1155/2019/1085717 |
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| author | Cornelia Thoeni Ruediger Waldherr Jutta Scheuerer Stefanie Schmitteckert Ralph Roeth Beate Niesler Ernest Cutz Christa Flechtenmacher Benjamin Goeppert Peter Schirmacher Felix Lasitschka |
| author_facet | Cornelia Thoeni Ruediger Waldherr Jutta Scheuerer Stefanie Schmitteckert Ralph Roeth Beate Niesler Ernest Cutz Christa Flechtenmacher Benjamin Goeppert Peter Schirmacher Felix Lasitschka |
| author_sort | Cornelia Thoeni |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ffd18f426e88469d80b64145c15bdaf8 |
| institution | Kabale University |
| issn | 2291-2789 2291-2797 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Canadian Journal of Gastroenterology and Hepatology |
| spelling | doaj-art-ffd18f426e88469d80b64145c15bdaf82025-02-03T01:00:24ZengWileyCanadian Journal of Gastroenterology and Hepatology2291-27892291-27972019-01-01201910.1155/2019/10857171085717Expression Analysis of ATP-Binding Cassette Transporters ABCB11 and ABCB4 in Primary Sclerosing Cholangitis and Variety of Pediatric and Adult Cholestatic and Noncholestatic Liver DiseasesCornelia Thoeni0Ruediger Waldherr1Jutta Scheuerer2Stefanie Schmitteckert3Ralph Roeth4Beate Niesler5Ernest Cutz6Christa Flechtenmacher7Benjamin Goeppert8Peter Schirmacher9Felix Lasitschka10Institute of Pathology, University Hospital Heidelberg, Heidelberg, GermanyInstitute of Pathology, University Hospital Heidelberg, Heidelberg, GermanyInstitute of Pathology, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Human Molecular Genetics, Institute of Human Genetics, University Heidelberg, Heidelberg, GermanyDepartment of Human Molecular Genetics, Institute of Human Genetics, University Heidelberg, Heidelberg, GermanyDepartment of Human Molecular Genetics, Institute of Human Genetics, University Heidelberg, Heidelberg, GermanyDivision of Pathology, Department of Paediatric Laboratory Medicine (DPLM), The Hospital for Sick Children, University of Toronto, Toronto, CanadaInstitute of Pathology, University Hospital Heidelberg, Heidelberg, GermanyInstitute of Pathology, University Hospital Heidelberg, Heidelberg, GermanyInstitute of Pathology, University Hospital Heidelberg, Heidelberg, GermanyInstitute of Pathology, University Hospital Heidelberg, Heidelberg, GermanyATP-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.http://dx.doi.org/10.1155/2019/1085717 |
| spellingShingle | Cornelia Thoeni Ruediger Waldherr Jutta Scheuerer Stefanie Schmitteckert Ralph Roeth Beate Niesler Ernest Cutz Christa Flechtenmacher Benjamin Goeppert Peter Schirmacher Felix Lasitschka Expression Analysis of ATP-Binding Cassette Transporters ABCB11 and ABCB4 in Primary Sclerosing Cholangitis and Variety of Pediatric and Adult Cholestatic and Noncholestatic Liver Diseases Canadian Journal of Gastroenterology and Hepatology |
| title | Expression Analysis of ATP-Binding Cassette Transporters ABCB11 and ABCB4 in Primary Sclerosing Cholangitis and Variety of Pediatric and Adult Cholestatic and Noncholestatic Liver Diseases |
| title_full | Expression Analysis of ATP-Binding Cassette Transporters ABCB11 and ABCB4 in Primary Sclerosing Cholangitis and Variety of Pediatric and Adult Cholestatic and Noncholestatic Liver Diseases |
| title_fullStr | Expression Analysis of ATP-Binding Cassette Transporters ABCB11 and ABCB4 in Primary Sclerosing Cholangitis and Variety of Pediatric and Adult Cholestatic and Noncholestatic Liver Diseases |
| title_full_unstemmed | Expression Analysis of ATP-Binding Cassette Transporters ABCB11 and ABCB4 in Primary Sclerosing Cholangitis and Variety of Pediatric and Adult Cholestatic and Noncholestatic Liver Diseases |
| title_short | Expression Analysis of ATP-Binding Cassette Transporters ABCB11 and ABCB4 in Primary Sclerosing Cholangitis and Variety of Pediatric and Adult Cholestatic and Noncholestatic Liver Diseases |
| title_sort | expression analysis of atp binding cassette transporters abcb11 and abcb4 in primary sclerosing cholangitis and variety of pediatric and adult cholestatic and noncholestatic liver diseases |
| url | http://dx.doi.org/10.1155/2019/1085717 |
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