Liver Expression of Sulphotransferase 2A1 Enzyme Is Impaired in Patients with Primary Sclerosing Cholangitis: Lack of the Response to Enhanced Expression of PXR
Background/Aim. Sulphotransferase 2A1 (SULT2A1) exerts hepatoprotective effects. Transcription of SULT2A1 gene is induced by pregnane-X-receptor (PXR) and can be repressed by miR-378a-5p. We studied the PXR/SULT2A1 axis in chronic cholestatic conditions: primary sclerosing cholangitis (PSC) and prim...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2015/571353 |
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| author | Ewa Wunsch Marta Klak Urszula Wasik Malgorzata Milkiewicz Malgorzata Blatkiewicz Elzbieta Urasinska Olivier Barbier Dariusz Bielicki Dimitrios P. Bogdanos Elwyn Elias Piotr Milkiewicz |
| author_facet | Ewa Wunsch Marta Klak Urszula Wasik Malgorzata Milkiewicz Malgorzata Blatkiewicz Elzbieta Urasinska Olivier Barbier Dariusz Bielicki Dimitrios P. Bogdanos Elwyn Elias Piotr Milkiewicz |
| author_sort | Ewa Wunsch |
| collection | DOAJ |
| description | Background/Aim. Sulphotransferase 2A1 (SULT2A1) exerts hepatoprotective effects. Transcription of SULT2A1 gene is induced by pregnane-X-receptor (PXR) and can be repressed by miR-378a-5p. We studied the PXR/SULT2A1 axis in chronic cholestatic conditions: primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Materials/Methods. Western-blot/PCRs for SULT2A1/PXR were performed in PSC (n=11), PBC (n=19), and control liver tissues (n=19). PXR and SULT2A1 mRNA was analyzed in intestinal tissues from 22 PSC patients. Genomic DNA was isolated from blood of PSC patients (n=120) and an equal number of healthy volunteers. Liver miRNA expression was evaluated using Affymetrix-Gene-Chip miRNA4.0. Results. Increased PXR protein was observed in both PSC and PBC compared to controls and was accompanied by a significant increase of SULT2A1 in PBC but not in PSC. Decreased expression of SULT2A1 mRNA was also seen in ileum of patients with PSC. Unlike PBC, miRNA analysis in PSC has shown a substantial increase in liver miR-378a-5p. Conclusions. PSC is characterized by disease-specific impairment of SULT2A1 expression following PXR activation, a phenomenon which is not noted in PBC, and may account for the impaired hepatoprotection in PSC. miRNA analysis suggests that SULT2A1 expression in PSC may be regulated by miR-378a-5p, connoting its pathogenic role. |
| format | Article |
| id | doaj-art-6a9e5759ddab4d3daf52c0a39afb2858 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-6a9e5759ddab4d3daf52c0a39afb28582025-02-03T01:12:13ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/571353571353Liver Expression of Sulphotransferase 2A1 Enzyme Is Impaired in Patients with Primary Sclerosing Cholangitis: Lack of the Response to Enhanced Expression of PXREwa Wunsch0Marta Klak1Urszula Wasik2Malgorzata Milkiewicz3Malgorzata Blatkiewicz4Elzbieta Urasinska5Olivier Barbier6Dariusz Bielicki7Dimitrios P. Bogdanos8Elwyn Elias9Piotr Milkiewicz10Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, 70-111 Szczecin, PolandDepartment of Medical Biology, Pomeranian Medical University, 70-111 Szczecin, PolandDepartment of Medical Biology, Pomeranian Medical University, 70-111 Szczecin, PolandDepartment of Medical Biology, Pomeranian Medical University, 70-111 Szczecin, PolandDepartment of Medical Biology, Pomeranian Medical University, 70-111 Szczecin, PolandDepartment of Pathology, Pomeranian Medical University, 71-252 Szczecin, PolandLaboratory of Molecular Pharmacology, CHU Québec and Faculty of Pharmacy, Laval University, Québec, QC, CanadaDepartment of Gastroenterology, Pomeranian Medical University, 71-252 Szczecin, PolandLiver Sciences, Division of Liver Transplantation and Mucosal Biology, King’s College London School of Medicine, Denmark Hill Campus, London SE5 9RS, UKLiver and Hepatobiliary Unit, Queen Elizabeth Hospital, University of Birmingham, Birmingham B15 2TT, UKDepartment of Clinical and Molecular Biochemistry, Pomeranian Medical University, 70-111 Szczecin, PolandBackground/Aim. Sulphotransferase 2A1 (SULT2A1) exerts hepatoprotective effects. Transcription of SULT2A1 gene is induced by pregnane-X-receptor (PXR) and can be repressed by miR-378a-5p. We studied the PXR/SULT2A1 axis in chronic cholestatic conditions: primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Materials/Methods. Western-blot/PCRs for SULT2A1/PXR were performed in PSC (n=11), PBC (n=19), and control liver tissues (n=19). PXR and SULT2A1 mRNA was analyzed in intestinal tissues from 22 PSC patients. Genomic DNA was isolated from blood of PSC patients (n=120) and an equal number of healthy volunteers. Liver miRNA expression was evaluated using Affymetrix-Gene-Chip miRNA4.0. Results. Increased PXR protein was observed in both PSC and PBC compared to controls and was accompanied by a significant increase of SULT2A1 in PBC but not in PSC. Decreased expression of SULT2A1 mRNA was also seen in ileum of patients with PSC. Unlike PBC, miRNA analysis in PSC has shown a substantial increase in liver miR-378a-5p. Conclusions. PSC is characterized by disease-specific impairment of SULT2A1 expression following PXR activation, a phenomenon which is not noted in PBC, and may account for the impaired hepatoprotection in PSC. miRNA analysis suggests that SULT2A1 expression in PSC may be regulated by miR-378a-5p, connoting its pathogenic role.http://dx.doi.org/10.1155/2015/571353 |
| spellingShingle | Ewa Wunsch Marta Klak Urszula Wasik Malgorzata Milkiewicz Malgorzata Blatkiewicz Elzbieta Urasinska Olivier Barbier Dariusz Bielicki Dimitrios P. Bogdanos Elwyn Elias Piotr Milkiewicz Liver Expression of Sulphotransferase 2A1 Enzyme Is Impaired in Patients with Primary Sclerosing Cholangitis: Lack of the Response to Enhanced Expression of PXR Journal of Immunology Research |
| title | Liver Expression of Sulphotransferase 2A1 Enzyme Is Impaired in Patients with Primary Sclerosing Cholangitis: Lack of the Response to Enhanced Expression of PXR |
| title_full | Liver Expression of Sulphotransferase 2A1 Enzyme Is Impaired in Patients with Primary Sclerosing Cholangitis: Lack of the Response to Enhanced Expression of PXR |
| title_fullStr | Liver Expression of Sulphotransferase 2A1 Enzyme Is Impaired in Patients with Primary Sclerosing Cholangitis: Lack of the Response to Enhanced Expression of PXR |
| title_full_unstemmed | Liver Expression of Sulphotransferase 2A1 Enzyme Is Impaired in Patients with Primary Sclerosing Cholangitis: Lack of the Response to Enhanced Expression of PXR |
| title_short | Liver Expression of Sulphotransferase 2A1 Enzyme Is Impaired in Patients with Primary Sclerosing Cholangitis: Lack of the Response to Enhanced Expression of PXR |
| title_sort | liver expression of sulphotransferase 2a1 enzyme is impaired in patients with primary sclerosing cholangitis lack of the response to enhanced expression of pxr |
| url | http://dx.doi.org/10.1155/2015/571353 |
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