Loss of detoxification in inflammatory bowel disease: dysregulation of pregnane X receptor target genes

Gastroenterology
Thomas LangmannGerd Schmitz

Abstract

Phase 1, phase 2, and cellular efflux transporters are critical components in intestinal barrier function against xenobiotics and bacteria. We therefore performed global gene expression profiling in patients with ulcerative colitis (UC) and Crohn's disease as well as control specimens, with a special emphasis on genes involved in detoxification and epithelial membrane integrity. Mucosal biopsy specimens from nonaffected regions of the colon and the terminal ileum were subjected to DNA microarray analysis and pathway-related data mining. Real-time reverse-transcription polymerase chain reaction was used for verification of selected regulated candidate genes in larger inflammatory bowel disease sample numbers and intestinal cell lines. Several dysregulated genes were identified in both disease groups and tissues. A set of genes coordinately down-regulated in the colon of patients with UC was composed of cellular detoxification and defense genes, which are target genes for the transcription factor pregnane X receptor (PXR). Messenger RNA expression of ABCB1 (MDR1) and PXR was significantly reduced in the colon of patients with UC but was unaffected in patients with Crohn's disease. In contrast to some of its target genes, the expr...Continue Reading

References

Mar 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J MårtenssonA Meister
Jul 1, 1988·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·G M PacificiG B Muraro
Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·R A HellerR W Davis
Apr 7, 1997·Biochemical and Biophysical Research Communications·H SchwerG Schmitz
Feb 14, 1998·Gut·W E Roediger, W Babidge
Apr 2, 1999·Alimentary Pharmacology & Therapeutics·M L ClapperS Murthy
Dec 21, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·H Suzuki, Y Sugiyama
Dec 26, 2001·Nucleic Acids Research·Yutaka SuzukiSumio Sugano
Jan 24, 2002·The Journal of Pharmacology and Experimental Therapeutics·Ronald N Hines, D Gail McCarver
Feb 8, 2003·Journal of Gastroenterology·Minoru ToyotaKohzoh Imai
Feb 15, 2003·Journal of Pharmaceutical Sciences·Hisashi IizasaEmi Nakashima
Mar 29, 2003·Toxicology and Applied Pharmacology·Guangping ChenAnna Radominska-Pandya
Apr 3, 2003·Gastroenterology·Tadakazu HisamatsuDaniel K Podolsky
May 30, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Akihide KamiyaFrank J Gonzalez
Jul 10, 2003·Gastroenterology·Emiko MizoguchiAtsushi Mizoguchi
Aug 7, 2003·Inflammatory Bowel Diseases·Atsushi MizoguchiAtul K Bhan
Aug 20, 2003·Biostatistics·C M KendziorskiA D Attie

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Citations

Jan 13, 2009·Inflammatory Bowel Diseases·Jonathan J HansenR Balfour Sartor
Oct 15, 2008·SAR and QSAR in Environmental Research·A KelE Wingender
Dec 5, 2008·Nutrition Reviews·Daniel R Schmidt, David J Mangelsdorf
Jul 16, 2010·The Journal of Pharmacology and Experimental Therapeutics·Jie ChengFrank J Gonzalez
Sep 22, 2006·Annual Review of Medicine·Judy H Cho, Clara Abraham
Feb 26, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·Seema SaksenaPradeep K Dudeja
Nov 3, 2012·PloS One·Daniel SlivaShailesh Dudhgaonkar
Nov 20, 2013·Drug Design, Development and Therapy·Daren LowEmiko Mizoguchi
Nov 21, 2008·Pharmacogenomics·Bin ZhangMatthew D Krasowski
Aug 2, 2012·American Journal of Veterinary Research·Vicki L WilkeAlbert E Jergens
Dec 15, 2010·International Journal of Molecular Sciences·Hannah SchneiderRobert Ehehalt
Jan 20, 2011·World Journal of Gastroenterology : WJG·Vibeke AndersenUlla Vogel
Jun 8, 2013·World Journal of Gastroenterology : WJG·Ying-Lei MiaoLi-Ping Duan
Jun 6, 2009·Journal of Carcinogenesis·Yumiko Yasui, Takuji Tanaka
Jan 31, 2014·Journal of Medicinal Food·Chukwuemezie ChimezieRobert E Stratford
Oct 17, 2013·Mucosal Immunology·G Pineton de ChambrunC Vignal
Jun 17, 2014·Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme·Emilienne Tudor Ngo SockJean-Marc Lavoie
Jun 15, 2007·Scandinavian Journal of Gastroenterology·Claudio CsillagOle Haagen Nielsen
Jul 3, 2015·Scandinavian Journal of Gastroenterology·Davide Giuseppe RibaldoneMarco Astegiano
Apr 25, 2007·Scandinavian Journal of Gastroenterology·Claudio CsillagRehannah Borup
Aug 21, 2012·Scandinavian Journal of Gastroenterology·Linda GillbergPer M Hellström
Dec 7, 2011·Expert Review of Clinical Pharmacology·Alexander M CressmanMicheline Piquette-Miller
Jul 5, 2008·Expert Review of Molecular Diagnostics·Marie-Alice MeuwisMarie-Paule Merville
Sep 1, 2008·Expert Review of Clinical Pharmacology·Guillaume DumaisPatrick du Souich
Dec 23, 2008·Expert Review of Molecular Diagnostics·Petra von Stein
May 25, 2013·Drug Metabolism Reviews·Susumu Kodama, Masahiko Negishi
Jun 10, 2009·Expert Opinion on Drug Metabolism & Toxicology·Satyanarayana R PondugulaTaosheng Chen
Jul 16, 2008·Expert Opinion on Drug Metabolism & Toxicology·Teruo Murakami, Mikihisa Takano

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