Regulation of organic anion transporters in a new rat model of acute and chronic cholangitis resembling human primary sclerosing cholangitis
Background/Aims: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease of unknown etiology. Although the primary defect affects cholangiocytes, cholestatic injury of hepatocytes may promote further liver damage. Since down-regulation of hepatocellular organic anion transporters is impl...
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| Veröffentlicht in: | Journal of hepatology 2002-06, Vol.36 (6), p.718-724 |
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| creator | Geier, Andreas Dietrich, Christoph G Lammert, Frank Orth, Thomas Mayet, Werner-Johannes Matern, Siegfried Gartung, Carsten |
| description | Background/Aims: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease of unknown etiology. Although the primary defect affects cholangiocytes, cholestatic injury of hepatocytes may promote further liver damage. Since down-regulation of hepatocellular organic anion transporters is implicated in the molecular pathogenesis of cholestasis, expression of these transporters was determined in a novel rat model, which closely resembles human PSC.
Methods: Hepatic protein and mRNA expression of basolateral (Ntcp, Oatp1, 2 and 4) and canalicular (Mrp2, Bsep) organic anion transporters were analyzed 1, 4 and 12 weeks after induction of experimental PSC by 2,4,6-trinitrobenzenesulfonic acid (TNBS).
Results: Specific down-regulation of basolateral and canalicular transport systems except Oatp4 and Bsep proteins occurred during the acute phase of inflammation. In chronic cholangitis 12 weeks after TNBS Mrp2 protein and mRNA remained down-regulated by 40–50% of controls (
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| doi_str_mv | 10.1016/S0168-8278(02)00052-1 |
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| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71765666</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0168827802000521</els_id><sourcerecordid>71765666</sourcerecordid><originalsourceid>FETCH-LOGICAL-c391t-b344769eb163fa836a56355a9a716653828ba8cc5a003ca9746a2e02b36d63a83</originalsourceid><addsrcrecordid>eNqFkcuO1DAQRS0EYnoGPgHkDWhYBPyInWQ1QiNe0khIPNZWxal0GyV2Yzsg_oGPxpmOGHZsypJ9ruvWLUKecPaSM65ffS6lrVrRtJdMvGCMKVHxe2THNWMV0zW_T3Z_kTNyntK3AknW1Q_JGResrpVgO_L7E-6XCbILnoaRhrgH7ywtpVzkCD4dQ8wYE3WeAvX4k0bIdA4DTqsA7JKx4AO1hxhWqT2ECfzeZZdoxIRzPzm_p4dlBk-P0c0Qf9FkJ4whrQ__8I_IgxGmhI-384J8ffvmy_X76ubjuw_Xr28qKzueq17WdaM77LmWI7RSg9JSKeig4Vor2Yq2h9ZaBWVgC11TaxDIRC_1oGURXJDnp3-PMXxfMGUzu2RxKj4wLMk0vNFKa11AdQJtMZsijmYbwHBm1jWY2zWYNWPDhLldg-FF93RrsPQzDneqLfcCPNsASBamsQRtXbrjpG5bLuvCXZ04LHH8cBhNsg69xcFFtNkMwf3Hyh8_qaZh</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>71765666</pqid></control><display><type>article</type><title>Regulation of organic anion transporters in a new rat model of acute and chronic cholangitis resembling human primary sclerosing cholangitis</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Geier, Andreas ; Dietrich, Christoph G ; Lammert, Frank ; Orth, Thomas ; Mayet, Werner-Johannes ; Matern, Siegfried ; Gartung, Carsten</creator><creatorcontrib>Geier, Andreas ; Dietrich, Christoph G ; Lammert, Frank ; Orth, Thomas ; Mayet, Werner-Johannes ; Matern, Siegfried ; Gartung, Carsten</creatorcontrib><description>Background/Aims: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease of unknown etiology. Although the primary defect affects cholangiocytes, cholestatic injury of hepatocytes may promote further liver damage. Since down-regulation of hepatocellular organic anion transporters is implicated in the molecular pathogenesis of cholestasis, expression of these transporters was determined in a novel rat model, which closely resembles human PSC.
Methods: Hepatic protein and mRNA expression of basolateral (Ntcp, Oatp1, 2 and 4) and canalicular (Mrp2, Bsep) organic anion transporters were analyzed 1, 4 and 12 weeks after induction of experimental PSC by 2,4,6-trinitrobenzenesulfonic acid (TNBS).
Results: Specific down-regulation of basolateral and canalicular transport systems except Oatp4 and Bsep proteins occurred during the acute phase of inflammation. In chronic cholangitis 12 weeks after TNBS Mrp2 protein and mRNA remained down-regulated by 40–50% of controls (
P<0.05). In addition Oatp1 protein was also reduced by 40±13% (
P<0.05), whereas all other transporters returned to control values.
Conclusions: In chronic cholangitis only canalicular Mrp2 expression remained down-regulated. This might represent the first injury to hepatocytes in chronic cholangitis as an extension of liver injury from the level of cholangiocytes to hepatocytes in PSC.</description><identifier>ISSN: 0168-8278</identifier><identifier>EISSN: 1600-0641</identifier><identifier>DOI: 10.1016/S0168-8278(02)00052-1</identifier><identifier>PMID: 12044520</identifier><identifier>CODEN: JOHEEC</identifier><language>eng</language><publisher>Oxford: Elsevier B.V</publisher><subject>Acute and chronic cholangitis ; Acute Disease ; Animals ; ATP-Binding Cassette Transporters ; Biological and medical sciences ; Carrier Proteins - genetics ; Cholangitis, Sclerosing - physiopathology ; Chronic Disease ; Digestive system ; Disease Models, Animal ; Female ; Gene Expression - physiology ; Human primary sclerosing cholangitis ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Medical sciences ; Membrane Transport Proteins ; Organic anion transporters ; Organic Anion Transporters, Sodium-Dependent ; Organic Anion Transporters, Sodium-Independent - genetics ; Organic Cation Transport Proteins - genetics ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Rats ; Rats, Inbred Lew ; RNA, Messenger - analysis ; Solute Carrier Organic Anion Transporter Family Member 1B3 ; Symporters</subject><ispartof>Journal of hepatology, 2002-06, Vol.36 (6), p.718-724</ispartof><rights>2002 European Association for the Study of the Liver</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-b344769eb163fa836a56355a9a716653828ba8cc5a003ca9746a2e02b36d63a83</citedby><cites>FETCH-LOGICAL-c391t-b344769eb163fa836a56355a9a716653828ba8cc5a003ca9746a2e02b36d63a83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0168827802000521$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13688134$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12044520$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Geier, Andreas</creatorcontrib><creatorcontrib>Dietrich, Christoph G</creatorcontrib><creatorcontrib>Lammert, Frank</creatorcontrib><creatorcontrib>Orth, Thomas</creatorcontrib><creatorcontrib>Mayet, Werner-Johannes</creatorcontrib><creatorcontrib>Matern, Siegfried</creatorcontrib><creatorcontrib>Gartung, Carsten</creatorcontrib><title>Regulation of organic anion transporters in a new rat model of acute and chronic cholangitis resembling human primary sclerosing cholangitis</title><title>Journal of hepatology</title><addtitle>J Hepatol</addtitle><description>Background/Aims: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease of unknown etiology. Although the primary defect affects cholangiocytes, cholestatic injury of hepatocytes may promote further liver damage. Since down-regulation of hepatocellular organic anion transporters is implicated in the molecular pathogenesis of cholestasis, expression of these transporters was determined in a novel rat model, which closely resembles human PSC.
Methods: Hepatic protein and mRNA expression of basolateral (Ntcp, Oatp1, 2 and 4) and canalicular (Mrp2, Bsep) organic anion transporters were analyzed 1, 4 and 12 weeks after induction of experimental PSC by 2,4,6-trinitrobenzenesulfonic acid (TNBS).
Results: Specific down-regulation of basolateral and canalicular transport systems except Oatp4 and Bsep proteins occurred during the acute phase of inflammation. In chronic cholangitis 12 weeks after TNBS Mrp2 protein and mRNA remained down-regulated by 40–50% of controls (
P<0.05). In addition Oatp1 protein was also reduced by 40±13% (
P<0.05), whereas all other transporters returned to control values.
Conclusions: In chronic cholangitis only canalicular Mrp2 expression remained down-regulated. This might represent the first injury to hepatocytes in chronic cholangitis as an extension of liver injury from the level of cholangiocytes to hepatocytes in PSC.</description><subject>Acute and chronic cholangitis</subject><subject>Acute Disease</subject><subject>Animals</subject><subject>ATP-Binding Cassette Transporters</subject><subject>Biological and medical sciences</subject><subject>Carrier Proteins - genetics</subject><subject>Cholangitis, Sclerosing - physiopathology</subject><subject>Chronic Disease</subject><subject>Digestive system</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Gene Expression - physiology</subject><subject>Human primary sclerosing cholangitis</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Transport Proteins</subject><subject>Organic anion transporters</subject><subject>Organic Anion Transporters, Sodium-Dependent</subject><subject>Organic Anion Transporters, Sodium-Independent - genetics</subject><subject>Organic Cation Transport Proteins - genetics</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>RNA, Messenger - analysis</subject><subject>Solute Carrier Organic Anion Transporter Family Member 1B3</subject><subject>Symporters</subject><issn>0168-8278</issn><issn>1600-0641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuO1DAQRS0EYnoGPgHkDWhYBPyInWQ1QiNe0khIPNZWxal0GyV2Yzsg_oGPxpmOGHZsypJ9ruvWLUKecPaSM65ffS6lrVrRtJdMvGCMKVHxe2THNWMV0zW_T3Z_kTNyntK3AknW1Q_JGResrpVgO_L7E-6XCbILnoaRhrgH7ywtpVzkCD4dQ8wYE3WeAvX4k0bIdA4DTqsA7JKx4AO1hxhWqT2ECfzeZZdoxIRzPzm_p4dlBk-P0c0Qf9FkJ4whrQ__8I_IgxGmhI-384J8ffvmy_X76ubjuw_Xr28qKzueq17WdaM77LmWI7RSg9JSKeig4Vor2Yq2h9ZaBWVgC11TaxDIRC_1oGURXJDnp3-PMXxfMGUzu2RxKj4wLMk0vNFKa11AdQJtMZsijmYbwHBm1jWY2zWYNWPDhLldg-FF93RrsPQzDneqLfcCPNsASBamsQRtXbrjpG5bLuvCXZ04LHH8cBhNsg69xcFFtNkMwf3Hyh8_qaZh</recordid><startdate>20020601</startdate><enddate>20020601</enddate><creator>Geier, Andreas</creator><creator>Dietrich, Christoph G</creator><creator>Lammert, Frank</creator><creator>Orth, Thomas</creator><creator>Mayet, Werner-Johannes</creator><creator>Matern, Siegfried</creator><creator>Gartung, Carsten</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20020601</creationdate><title>Regulation of organic anion transporters in a new rat model of acute and chronic cholangitis resembling human primary sclerosing cholangitis</title><author>Geier, Andreas ; Dietrich, Christoph G ; Lammert, Frank ; Orth, Thomas ; Mayet, Werner-Johannes ; Matern, Siegfried ; Gartung, Carsten</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-b344769eb163fa836a56355a9a716653828ba8cc5a003ca9746a2e02b36d63a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Acute and chronic cholangitis</topic><topic>Acute Disease</topic><topic>Animals</topic><topic>ATP-Binding Cassette Transporters</topic><topic>Biological and medical sciences</topic><topic>Carrier Proteins - genetics</topic><topic>Cholangitis, Sclerosing - physiopathology</topic><topic>Chronic Disease</topic><topic>Digestive system</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Gene Expression - physiology</topic><topic>Human primary sclerosing cholangitis</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Transport Proteins</topic><topic>Organic anion transporters</topic><topic>Organic Anion Transporters, Sodium-Dependent</topic><topic>Organic Anion Transporters, Sodium-Independent - genetics</topic><topic>Organic Cation Transport Proteins - genetics</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Rats</topic><topic>Rats, Inbred Lew</topic><topic>RNA, Messenger - analysis</topic><topic>Solute Carrier Organic Anion Transporter Family Member 1B3</topic><topic>Symporters</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Geier, Andreas</creatorcontrib><creatorcontrib>Dietrich, Christoph G</creatorcontrib><creatorcontrib>Lammert, Frank</creatorcontrib><creatorcontrib>Orth, Thomas</creatorcontrib><creatorcontrib>Mayet, Werner-Johannes</creatorcontrib><creatorcontrib>Matern, Siegfried</creatorcontrib><creatorcontrib>Gartung, Carsten</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Geier, Andreas</au><au>Dietrich, Christoph G</au><au>Lammert, Frank</au><au>Orth, Thomas</au><au>Mayet, Werner-Johannes</au><au>Matern, Siegfried</au><au>Gartung, Carsten</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of organic anion transporters in a new rat model of acute and chronic cholangitis resembling human primary sclerosing cholangitis</atitle><jtitle>Journal of hepatology</jtitle><addtitle>J Hepatol</addtitle><date>2002-06-01</date><risdate>2002</risdate><volume>36</volume><issue>6</issue><spage>718</spage><epage>724</epage><pages>718-724</pages><issn>0168-8278</issn><eissn>1600-0641</eissn><coden>JOHEEC</coden><abstract>Background/Aims: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease of unknown etiology. Although the primary defect affects cholangiocytes, cholestatic injury of hepatocytes may promote further liver damage. Since down-regulation of hepatocellular organic anion transporters is implicated in the molecular pathogenesis of cholestasis, expression of these transporters was determined in a novel rat model, which closely resembles human PSC.
Methods: Hepatic protein and mRNA expression of basolateral (Ntcp, Oatp1, 2 and 4) and canalicular (Mrp2, Bsep) organic anion transporters were analyzed 1, 4 and 12 weeks after induction of experimental PSC by 2,4,6-trinitrobenzenesulfonic acid (TNBS).
Results: Specific down-regulation of basolateral and canalicular transport systems except Oatp4 and Bsep proteins occurred during the acute phase of inflammation. In chronic cholangitis 12 weeks after TNBS Mrp2 protein and mRNA remained down-regulated by 40–50% of controls (
P<0.05). In addition Oatp1 protein was also reduced by 40±13% (
P<0.05), whereas all other transporters returned to control values.
Conclusions: In chronic cholangitis only canalicular Mrp2 expression remained down-regulated. This might represent the first injury to hepatocytes in chronic cholangitis as an extension of liver injury from the level of cholangiocytes to hepatocytes in PSC.</abstract><cop>Oxford</cop><pub>Elsevier B.V</pub><pmid>12044520</pmid><doi>10.1016/S0168-8278(02)00052-1</doi><tpages>7</tpages></addata></record> |
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| subjects | Acute and chronic cholangitis Acute Disease Animals ATP-Binding Cassette Transporters Biological and medical sciences Carrier Proteins - genetics Cholangitis, Sclerosing - physiopathology Chronic Disease Digestive system Disease Models, Animal Female Gene Expression - physiology Human primary sclerosing cholangitis Investigative techniques, diagnostic techniques (general aspects) Male Medical sciences Membrane Transport Proteins Organic anion transporters Organic Anion Transporters, Sodium-Dependent Organic Anion Transporters, Sodium-Independent - genetics Organic Cation Transport Proteins - genetics Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Rats Rats, Inbred Lew RNA, Messenger - analysis Solute Carrier Organic Anion Transporter Family Member 1B3 Symporters |
| title | Regulation of organic anion transporters in a new rat model of acute and chronic cholangitis resembling human primary sclerosing cholangitis |
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