Bile acids directly augment caudal related homeobox gene Cdx2 expression in oesophageal keratinocytes in Barrett’s epithelium
Background and aims: The mechanism of transformation to intestinal metaplasia in Barrett’s oesophagus has not been clarified. We investigated the effects of various bile acids on expression of the caudal related homeobox gene Cdx2 in cultured oesophageal squamous epithelial cells. In addition, morph...
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| description | Background and aims: The mechanism of transformation to intestinal metaplasia in Barrett’s oesophagus has not been clarified. We investigated the effects of various bile acids on expression of the caudal related homeobox gene Cdx2 in cultured oesophageal squamous epithelial cells. In addition, morphological and histochemical changes in squamous cells to intestinal epithelial cells were studied in response to bile acid induced expression of Cdx2. Methods: A rat model of Barrett’s oesophagus was created by anastomosing the oesophagus and jejunum, and Cdx2 expression was investigated by immunohistochemistry. Also, the response of various bile acids on Cdx2 gene expression was studied in the human colon epithelial cell lines Caco-2 and HT-29, as well as in cultured rat oesophageal squamous epithelial cells using a Cdx2 promoter luciferase assay. In addition, primary cultured oesophageal squamous epithelial cells were transfected with Cdx2 expression vectors and their possible transformation to intestinal-type epithelial cells was investigated. Results: Oesophagojejunal anastomoses formed intestinal goblet cell metaplasia in rat oesophagus specimens and metaplastic epithelia strongly expressed Cdx2. When the effects of 11 types of bile acids on Cdx2 gene expression were examined, only cholic acid (CA) and dehydrocholic acid dose dependently increased Cdx2 promoter activity and Cdx2 protein production in Caco-2 and HT-29 cells, and cultured rat oesophageal keratinocytes. Results from mutation analysis of Cdx2 promoter suggested that two nuclear factor κB (NFκB) binding sites were responsible for the bile acid induced activation of the Cdx2 promoter. When bile acids were measured in oesophageal refluxate of rats with experimental Barrett’s oesophagus, the concentration of CA was found to be consistent with the experimental dose that augmented Cdx2 expression in vitro. Furthermore, transfection of the Cdx2 expression vector in cultured rat oesophageal keratinocytes induced production of intestinal-type mucin, MUC2, in cells that expressed Cdx2. Conclusions: We found that CA activates Cdx2 promoter via NFκB and stimulates production of Cdx2 protein in oesophageal keratinocytes with production of intestinal-type mucin. This may be one of the mechanisms of metaplasia in Barrett’s oesophagus. |
| doi_str_mv | 10.1136/gut.2005.066209 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1856383</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>70200612</sourcerecordid><originalsourceid>FETCH-LOGICAL-b663t-5864c81d9092eae1fa2b860ca283f8763da85943d07f2a073a7e6ccbba84ff223</originalsourceid><addsrcrecordid>eNqFks-O0zAQxiMEYsvCmRuKhOCA1K7_JLZzWYlWsIBWcAEOe7EmzqR1N4mL7aD2BK_B6_EkuGq1C1z2ZEvzm0_zzXxZ9pSSGaVcnC3HOGOElDMiBCPVvWxCC6GmnCl1P5sQQuW0lEV1kj0KYU0IUaqiD7MTKihVvFCT7MfcdpiDsU3IG-vRxG6Xw7jscYi5gbGBLvfYQcQmX7keXe22-RIHzBfNluW43XgMwboht0PuMLjNCpaYmq7RQ7SDM7uIYV-cg_cY4--fv0KOGxtX2Nmxf5w9aKEL-OT4nmZf3r75vHg3vfx08X7x-nJaC8HjtFSiMIo2FakYAtIWWK0EMcAUb5UUvAFVVgVviGwZEMlBojCmrkEVbcsYP83OD7qbse6xMcmeh05vvO3B77QDq_-tDHall-67pqoUXPEk8PIo4N23EUPUvQ0Guw4GdGPQkqQ7CMruBBlRBSlJmcDn_4FrN_ohbUFTKSvOy5JWiTo7UMa7EDy2NzNTovcZ0CkDep8BfchA6nj2t9Vb_nj0BLw4AhAMdK2Hwdhwy8mCVITuLU8PnA0Rtzd18NdaSC5L_fHrQl99mF9ckSp9Ev_qwNf9-s4p_wBU6toU</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1779335519</pqid></control><display><type>article</type><title>Bile acids directly augment caudal related homeobox gene Cdx2 expression in oesophageal keratinocytes in Barrett’s epithelium</title><source>MEDLINE</source><source>BMJ Journals - NESLi2</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Kazumori, H ; Ishihara, S ; Rumi, M A K ; Kadowaki, Y ; Kinoshita, Y</creator><creatorcontrib>Kazumori, H ; Ishihara, S ; Rumi, M A K ; Kadowaki, Y ; Kinoshita, Y</creatorcontrib><description>Background and aims: The mechanism of transformation to intestinal metaplasia in Barrett’s oesophagus has not been clarified. We investigated the effects of various bile acids on expression of the caudal related homeobox gene Cdx2 in cultured oesophageal squamous epithelial cells. In addition, morphological and histochemical changes in squamous cells to intestinal epithelial cells were studied in response to bile acid induced expression of Cdx2. Methods: A rat model of Barrett’s oesophagus was created by anastomosing the oesophagus and jejunum, and Cdx2 expression was investigated by immunohistochemistry. Also, the response of various bile acids on Cdx2 gene expression was studied in the human colon epithelial cell lines Caco-2 and HT-29, as well as in cultured rat oesophageal squamous epithelial cells using a Cdx2 promoter luciferase assay. In addition, primary cultured oesophageal squamous epithelial cells were transfected with Cdx2 expression vectors and their possible transformation to intestinal-type epithelial cells was investigated. Results: Oesophagojejunal anastomoses formed intestinal goblet cell metaplasia in rat oesophagus specimens and metaplastic epithelia strongly expressed Cdx2. When the effects of 11 types of bile acids on Cdx2 gene expression were examined, only cholic acid (CA) and dehydrocholic acid dose dependently increased Cdx2 promoter activity and Cdx2 protein production in Caco-2 and HT-29 cells, and cultured rat oesophageal keratinocytes. Results from mutation analysis of Cdx2 promoter suggested that two nuclear factor κB (NFκB) binding sites were responsible for the bile acid induced activation of the Cdx2 promoter. When bile acids were measured in oesophageal refluxate of rats with experimental Barrett’s oesophagus, the concentration of CA was found to be consistent with the experimental dose that augmented Cdx2 expression in vitro. Furthermore, transfection of the Cdx2 expression vector in cultured rat oesophageal keratinocytes induced production of intestinal-type mucin, MUC2, in cells that expressed Cdx2. Conclusions: We found that CA activates Cdx2 promoter via NFκB and stimulates production of Cdx2 protein in oesophageal keratinocytes with production of intestinal-type mucin. This may be one of the mechanisms of metaplasia in Barrett’s oesophagus.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>DOI: 10.1136/gut.2005.066209</identifier><identifier>PMID: 16118348</identifier><identifier>CODEN: GUTTAK</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and British Society of Gastroenterology</publisher><subject>Acids ; Animals ; Barrett Esophagus - metabolism ; Barrett Esophagus - pathology ; Barrett’s oesophagus ; Bile ; bile acid ; Bile Acids and Salts - analysis ; Bile Acids and Salts - pharmacology ; Biological and medical sciences ; Blotting, Northern ; CDCA ; Cdx2 ; CDX2 Transcription Factor ; Cells, Cultured ; chenodeoxycholic acid ; cholic acid ; Cholic Acid - pharmacology ; cytokeratin ; DCA ; dehydrocholic acid ; deoxycholic acid ; DHCA ; Disease Models, Animal ; electrophoretic mobility shift assay ; EMSA ; Esophagus ; gastro-oesophageal reflux disease ; Gastroenterology. Liver. Pancreas. Abdomen ; Gastrointestinal Contents - chemistry ; GCA ; GCANa ; GCDCA ; Gene Expression Regulation - drug effects ; Genes, Homeobox - drug effects ; Genes, Reporter ; glycochenodeoxycholic acid ; glycocholic acid ; GORD ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Humans ; Keratinocytes - drug effects ; Keratinocytes - metabolism ; kilobase ; LCA ; lithocholic acid ; Male ; Medical sciences ; NFκB ; nuclear factor κB ; Oesophagus ; Other diseases. Semiology ; Promoter Regions, Genetic ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction - methods ; reverse transcription-polymerase chain reaction ; Rodents ; RT-PCR ; Small intestine ; sodium salt ; Studies ; taurochenodeoxycholic acid ; taurocholic acid ; taurodeoxycholic acid ; TCA ; TCDCA ; TDCA</subject><ispartof>Gut, 2006-01, Vol.55 (1), p.16-25</ispartof><rights>Copyright 2006 by Gut</rights><rights>2006 INIST-CNRS</rights><rights>Copyright: 2006 Copyright 2006 by Gut</rights><rights>Copyright © 2006 BMJ Publishing Group & British Society of Gastroenterology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b663t-5864c81d9092eae1fa2b860ca283f8763da85943d07f2a073a7e6ccbba84ff223</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://gut.bmj.com/content/55/1/16.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://gut.bmj.com/content/55/1/16.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,230,314,727,780,784,885,3195,4023,23570,27922,27923,27924,53790,53792,77471,77502</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17409013$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16118348$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kazumori, H</creatorcontrib><creatorcontrib>Ishihara, S</creatorcontrib><creatorcontrib>Rumi, M A K</creatorcontrib><creatorcontrib>Kadowaki, Y</creatorcontrib><creatorcontrib>Kinoshita, Y</creatorcontrib><title>Bile acids directly augment caudal related homeobox gene Cdx2 expression in oesophageal keratinocytes in Barrett’s epithelium</title><title>Gut</title><addtitle>Gut</addtitle><description>Background and aims: The mechanism of transformation to intestinal metaplasia in Barrett’s oesophagus has not been clarified. We investigated the effects of various bile acids on expression of the caudal related homeobox gene Cdx2 in cultured oesophageal squamous epithelial cells. In addition, morphological and histochemical changes in squamous cells to intestinal epithelial cells were studied in response to bile acid induced expression of Cdx2. Methods: A rat model of Barrett’s oesophagus was created by anastomosing the oesophagus and jejunum, and Cdx2 expression was investigated by immunohistochemistry. Also, the response of various bile acids on Cdx2 gene expression was studied in the human colon epithelial cell lines Caco-2 and HT-29, as well as in cultured rat oesophageal squamous epithelial cells using a Cdx2 promoter luciferase assay. In addition, primary cultured oesophageal squamous epithelial cells were transfected with Cdx2 expression vectors and their possible transformation to intestinal-type epithelial cells was investigated. Results: Oesophagojejunal anastomoses formed intestinal goblet cell metaplasia in rat oesophagus specimens and metaplastic epithelia strongly expressed Cdx2. When the effects of 11 types of bile acids on Cdx2 gene expression were examined, only cholic acid (CA) and dehydrocholic acid dose dependently increased Cdx2 promoter activity and Cdx2 protein production in Caco-2 and HT-29 cells, and cultured rat oesophageal keratinocytes. Results from mutation analysis of Cdx2 promoter suggested that two nuclear factor κB (NFκB) binding sites were responsible for the bile acid induced activation of the Cdx2 promoter. When bile acids were measured in oesophageal refluxate of rats with experimental Barrett’s oesophagus, the concentration of CA was found to be consistent with the experimental dose that augmented Cdx2 expression in vitro. Furthermore, transfection of the Cdx2 expression vector in cultured rat oesophageal keratinocytes induced production of intestinal-type mucin, MUC2, in cells that expressed Cdx2. Conclusions: We found that CA activates Cdx2 promoter via NFκB and stimulates production of Cdx2 protein in oesophageal keratinocytes with production of intestinal-type mucin. This may be one of the mechanisms of metaplasia in Barrett’s oesophagus.</description><subject>Acids</subject><subject>Animals</subject><subject>Barrett Esophagus - metabolism</subject><subject>Barrett Esophagus - pathology</subject><subject>Barrett’s oesophagus</subject><subject>Bile</subject><subject>bile acid</subject><subject>Bile Acids and Salts - analysis</subject><subject>Bile Acids and Salts - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>CDCA</subject><subject>Cdx2</subject><subject>CDX2 Transcription Factor</subject><subject>Cells, Cultured</subject><subject>chenodeoxycholic acid</subject><subject>cholic acid</subject><subject>Cholic Acid - pharmacology</subject><subject>cytokeratin</subject><subject>DCA</subject><subject>dehydrocholic acid</subject><subject>deoxycholic acid</subject><subject>DHCA</subject><subject>Disease Models, Animal</subject><subject>electrophoretic mobility shift assay</subject><subject>EMSA</subject><subject>Esophagus</subject><subject>gastro-oesophageal reflux disease</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gastrointestinal Contents - chemistry</subject><subject>GCA</subject><subject>GCANa</subject><subject>GCDCA</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Genes, Homeobox - drug effects</subject><subject>Genes, Reporter</subject><subject>glycochenodeoxycholic acid</subject><subject>glycocholic acid</subject><subject>GORD</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Keratinocytes - drug effects</subject><subject>Keratinocytes - metabolism</subject><subject>kilobase</subject><subject>LCA</subject><subject>lithocholic acid</subject><subject>Male</subject><subject>Medical sciences</subject><subject>NFκB</subject><subject>nuclear factor κB</subject><subject>Oesophagus</subject><subject>Other diseases. Semiology</subject><subject>Promoter Regions, Genetic</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Reverse Transcriptase Polymerase Chain Reaction - methods</subject><subject>reverse transcription-polymerase chain reaction</subject><subject>Rodents</subject><subject>RT-PCR</subject><subject>Small intestine</subject><subject>sodium salt</subject><subject>Studies</subject><subject>taurochenodeoxycholic acid</subject><subject>taurocholic acid</subject><subject>taurodeoxycholic acid</subject><subject>TCA</subject><subject>TCDCA</subject><subject>TDCA</subject><issn>0017-5749</issn><issn>1468-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFks-O0zAQxiMEYsvCmRuKhOCA1K7_JLZzWYlWsIBWcAEOe7EmzqR1N4mL7aD2BK_B6_EkuGq1C1z2ZEvzm0_zzXxZ9pSSGaVcnC3HOGOElDMiBCPVvWxCC6GmnCl1P5sQQuW0lEV1kj0KYU0IUaqiD7MTKihVvFCT7MfcdpiDsU3IG-vRxG6Xw7jscYi5gbGBLvfYQcQmX7keXe22-RIHzBfNluW43XgMwboht0PuMLjNCpaYmq7RQ7SDM7uIYV-cg_cY4--fv0KOGxtX2Nmxf5w9aKEL-OT4nmZf3r75vHg3vfx08X7x-nJaC8HjtFSiMIo2FakYAtIWWK0EMcAUb5UUvAFVVgVviGwZEMlBojCmrkEVbcsYP83OD7qbse6xMcmeh05vvO3B77QDq_-tDHall-67pqoUXPEk8PIo4N23EUPUvQ0Guw4GdGPQkqQ7CMruBBlRBSlJmcDn_4FrN_ohbUFTKSvOy5JWiTo7UMa7EDy2NzNTovcZ0CkDep8BfchA6nj2t9Vb_nj0BLw4AhAMdK2Hwdhwy8mCVITuLU8PnA0Rtzd18NdaSC5L_fHrQl99mF9ckSp9Ev_qwNf9-s4p_wBU6toU</recordid><startdate>200601</startdate><enddate>200601</enddate><creator>Kazumori, H</creator><creator>Ishihara, S</creator><creator>Rumi, M A K</creator><creator>Kadowaki, Y</creator><creator>Kinoshita, Y</creator><general>BMJ Publishing Group Ltd and British Society of Gastroenterology</general><general>BMJ</general><general>BMJ Publishing Group LTD</general><general>BMJ Group</general><scope>BSCLL</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200601</creationdate><title>Bile acids directly augment caudal related homeobox gene Cdx2 expression in oesophageal keratinocytes in Barrett’s epithelium</title><author>Kazumori, H ; Ishihara, S ; Rumi, M A K ; Kadowaki, Y ; Kinoshita, Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b663t-5864c81d9092eae1fa2b860ca283f8763da85943d07f2a073a7e6ccbba84ff223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Acids</topic><topic>Animals</topic><topic>Barrett Esophagus - metabolism</topic><topic>Barrett Esophagus - pathology</topic><topic>Barrett’s oesophagus</topic><topic>Bile</topic><topic>bile acid</topic><topic>Bile Acids and Salts - analysis</topic><topic>Bile Acids and Salts - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blotting, Northern</topic><topic>CDCA</topic><topic>Cdx2</topic><topic>CDX2 Transcription Factor</topic><topic>Cells, Cultured</topic><topic>chenodeoxycholic acid</topic><topic>cholic acid</topic><topic>Cholic Acid - pharmacology</topic><topic>cytokeratin</topic><topic>DCA</topic><topic>dehydrocholic acid</topic><topic>deoxycholic acid</topic><topic>DHCA</topic><topic>Disease Models, Animal</topic><topic>electrophoretic mobility shift assay</topic><topic>EMSA</topic><topic>Esophagus</topic><topic>gastro-oesophageal reflux disease</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gastrointestinal Contents - chemistry</topic><topic>GCA</topic><topic>GCANa</topic><topic>GCDCA</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Genes, Homeobox - drug effects</topic><topic>Genes, Reporter</topic><topic>glycochenodeoxycholic acid</topic><topic>glycocholic acid</topic><topic>GORD</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>Keratinocytes - drug effects</topic><topic>Keratinocytes - metabolism</topic><topic>kilobase</topic><topic>LCA</topic><topic>lithocholic acid</topic><topic>Male</topic><topic>Medical sciences</topic><topic>NFκB</topic><topic>nuclear factor κB</topic><topic>Oesophagus</topic><topic>Other diseases. Semiology</topic><topic>Promoter Regions, Genetic</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Reverse Transcriptase Polymerase Chain Reaction - methods</topic><topic>reverse transcription-polymerase chain reaction</topic><topic>Rodents</topic><topic>RT-PCR</topic><topic>Small intestine</topic><topic>sodium salt</topic><topic>Studies</topic><topic>taurochenodeoxycholic acid</topic><topic>taurocholic acid</topic><topic>taurodeoxycholic acid</topic><topic>TCA</topic><topic>TCDCA</topic><topic>TDCA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kazumori, H</creatorcontrib><creatorcontrib>Ishihara, S</creatorcontrib><creatorcontrib>Rumi, M A K</creatorcontrib><creatorcontrib>Kadowaki, Y</creatorcontrib><creatorcontrib>Kinoshita, Y</creatorcontrib><collection>Istex</collection><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>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Gut</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kazumori, H</au><au>Ishihara, S</au><au>Rumi, M A K</au><au>Kadowaki, Y</au><au>Kinoshita, Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bile acids directly augment caudal related homeobox gene Cdx2 expression in oesophageal keratinocytes in Barrett’s epithelium</atitle><jtitle>Gut</jtitle><addtitle>Gut</addtitle><date>2006-01</date><risdate>2006</risdate><volume>55</volume><issue>1</issue><spage>16</spage><epage>25</epage><pages>16-25</pages><issn>0017-5749</issn><eissn>1468-3288</eissn><coden>GUTTAK</coden><abstract>Background and aims: The mechanism of transformation to intestinal metaplasia in Barrett’s oesophagus has not been clarified. We investigated the effects of various bile acids on expression of the caudal related homeobox gene Cdx2 in cultured oesophageal squamous epithelial cells. In addition, morphological and histochemical changes in squamous cells to intestinal epithelial cells were studied in response to bile acid induced expression of Cdx2. Methods: A rat model of Barrett’s oesophagus was created by anastomosing the oesophagus and jejunum, and Cdx2 expression was investigated by immunohistochemistry. Also, the response of various bile acids on Cdx2 gene expression was studied in the human colon epithelial cell lines Caco-2 and HT-29, as well as in cultured rat oesophageal squamous epithelial cells using a Cdx2 promoter luciferase assay. In addition, primary cultured oesophageal squamous epithelial cells were transfected with Cdx2 expression vectors and their possible transformation to intestinal-type epithelial cells was investigated. Results: Oesophagojejunal anastomoses formed intestinal goblet cell metaplasia in rat oesophagus specimens and metaplastic epithelia strongly expressed Cdx2. When the effects of 11 types of bile acids on Cdx2 gene expression were examined, only cholic acid (CA) and dehydrocholic acid dose dependently increased Cdx2 promoter activity and Cdx2 protein production in Caco-2 and HT-29 cells, and cultured rat oesophageal keratinocytes. Results from mutation analysis of Cdx2 promoter suggested that two nuclear factor κB (NFκB) binding sites were responsible for the bile acid induced activation of the Cdx2 promoter. When bile acids were measured in oesophageal refluxate of rats with experimental Barrett’s oesophagus, the concentration of CA was found to be consistent with the experimental dose that augmented Cdx2 expression in vitro. Furthermore, transfection of the Cdx2 expression vector in cultured rat oesophageal keratinocytes induced production of intestinal-type mucin, MUC2, in cells that expressed Cdx2. Conclusions: We found that CA activates Cdx2 promoter via NFκB and stimulates production of Cdx2 protein in oesophageal keratinocytes with production of intestinal-type mucin. This may be one of the mechanisms of metaplasia in Barrett’s oesophagus.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and British Society of Gastroenterology</pub><pmid>16118348</pmid><doi>10.1136/gut.2005.066209</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Gut, 2006-01, Vol.55 (1), p.16-25 |
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| source | MEDLINE; BMJ Journals - NESLi2; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Acids Animals Barrett Esophagus - metabolism Barrett Esophagus - pathology Barrett’s oesophagus Bile bile acid Bile Acids and Salts - analysis Bile Acids and Salts - pharmacology Biological and medical sciences Blotting, Northern CDCA Cdx2 CDX2 Transcription Factor Cells, Cultured chenodeoxycholic acid cholic acid Cholic Acid - pharmacology cytokeratin DCA dehydrocholic acid deoxycholic acid DHCA Disease Models, Animal electrophoretic mobility shift assay EMSA Esophagus gastro-oesophageal reflux disease Gastroenterology. Liver. Pancreas. Abdomen Gastrointestinal Contents - chemistry GCA GCANa GCDCA Gene Expression Regulation - drug effects Genes, Homeobox - drug effects Genes, Reporter glycochenodeoxycholic acid glycocholic acid GORD Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans Keratinocytes - drug effects Keratinocytes - metabolism kilobase LCA lithocholic acid Male Medical sciences NFκB nuclear factor κB Oesophagus Other diseases. Semiology Promoter Regions, Genetic Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction - methods reverse transcription-polymerase chain reaction Rodents RT-PCR Small intestine sodium salt Studies taurochenodeoxycholic acid taurocholic acid taurodeoxycholic acid TCA TCDCA TDCA |
| title | Bile acids directly augment caudal related homeobox gene Cdx2 expression in oesophageal keratinocytes in Barrett’s epithelium |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T10%3A52%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Bile%20acids%20directly%20augment%20caudal%20related%20homeobox%20gene%20Cdx2%20expression%20in%20oesophageal%20keratinocytes%20in%20Barrett%E2%80%99s%20epithelium&rft.jtitle=Gut&rft.au=Kazumori,%20H&rft.date=2006-01&rft.volume=55&rft.issue=1&rft.spage=16&rft.epage=25&rft.pages=16-25&rft.issn=0017-5749&rft.eissn=1468-3288&rft.coden=GUTTAK&rft_id=info:doi/10.1136/gut.2005.066209&rft_dat=%3Cproquest_pubme%3E70200612%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1779335519&rft_id=info:pmid/16118348&rfr_iscdi=true |