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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Jahnel, J; Fickert, P; Hauer, AC; Högenauer, C; Avian, A; Trauner, M.
Inflammatory bowel disease alters intestinal bile acid transporter expression.
Drug Metab Dispos. 2014; 42(9):1423-1431
Doi: 10.1124/dmd.114.058065
[OPEN ACCESS]
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PubMed
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- Führende Autor*innen der Med Uni Graz
- Jahnel Jörg
- Trauner Michael
- Co-Autor*innen der Med Uni Graz
- Avian Alexander
- Fickert Peter
- Hauer Almuthe
- Hoegenauer Christoph
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- Abstract:
- The enterohepatic circulation of bile acids (BAs) critically depends on absorption of BA in the terminal ileum and colon, which can be affected by inflammatory bowel disease (IBD). Diarrhea in IBD is believed to result in part from BA malabsorption (BAM). We explored whether IBD alters mRNA expression of key intestinal BA transporters, BA detoxifying systems, and nuclear receptors that regulate BA transport and detoxification. Using real-time polymerase chain reaction, mucosal biopsy specimens from the terminal ileum in Crohn's disease (CD) patients and from the descending colon in ulcerative colitis (UC) patients were assessed for mRNA expression. Levels were compared with healthy controls. The main ileal BA uptake transporter, the apical sodium dependent bile acid transporter, was downregulated in active CD and UC and in CD in remission. Other significant changes such as repression of breast cancer-related protein and sulphotransferase 2A1 were seen only during active disease. In UC, pancolitis (but not exclusively left-sided colitis) was associated with altered expression of major BA transporters [multidrug resistance-associated protein 3 (MRP3), MRP4, multidrug resistance gene 1, organic solute transporter α/β] and nuclear receptors (pregnane X receptor, vitamin D receptor) in the descending colon. UC pancolitis leads to broad changes and CD ileitis to selective changes in intestinal BA transporter expression. Early medical manipulation of intestinal BA transporters may help prevent BAM. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Bile Acids and Salts - genetics Bile Acids and Salts - metabolism
- Biopsy - methods
- Carrier Proteins - genetics Carrier Proteins - metabolism
- Case-Control Studies -
- Colitis, Ulcerative - genetics Colitis, Ulcerative - metabolism
- Colon - metabolism
- Down-Regulation - genetics
- Female -
- Humans -
- Ileum - metabolism
- Inflammatory Bowel Diseases - genetics Inflammatory Bowel Diseases - metabolism
- Male -
- Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism
- Membrane Transport Proteins - genetics Membrane Transport Proteins - metabolism
- Middle Aged -
- Organic Anion Transporters, Sodium-Dependent - genetics Organic Anion Transporters, Sodium-Dependent - metabolism
- RNA, Messenger - genetics
- Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - metabolism
- Symporters - genetics Symporters - metabolism