Jahnel Jörg, Fickert Peter, Hauer Almuthe C, Högenauer Christoph, Avian Alexander, Trauner Michael
Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine (J.J., P.F., C.H., M.T.), Department of Paediatrics and Adolescent Medicine (J.J., A.C.H.), and Institute for Medical Informatics, Statistics and Documentation (A.A.), Medical University Graz, Graz, Austria; and Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria (M.T.)
Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine (J.J., P.F., C.H., M.T.), Department of Paediatrics and Adolescent Medicine (J.J., A.C.H.), and Institute for Medical Informatics, Statistics and Documentation (A.A.), Medical University Graz, Graz, Austria; and Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria (M.T.).
Drug Metab Dispos. 2014 Sep;42(9):1423-31. doi: 10.1124/dmd.114.058065. Epub 2014 Jun 25.
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.
胆汁酸（BAs）的肠肝循环严重依赖于末端回肠和结肠中胆汁酸的吸收，而这可能会受到炎症性肠病（IBD）的影响。IBD中的腹泻被认为部分是由胆汁酸吸收不良（BAM）导致的。我们探究了IBD是否会改变关键肠道胆汁酸转运蛋白、胆汁酸解毒系统以及调节胆汁酸转运和解毒的核受体的mRNA表达。使用实时聚合酶链反应，对克罗恩病（CD）患者末端回肠和溃疡性结肠炎（UC）患者降结肠的黏膜活检标本进行mRNA表达评估。将这些水平与健康对照进行比较。主要的回肠胆汁酸摄取转运蛋白，即顶端钠依赖性胆汁酸转运蛋白，在活动期CD和UC以及缓解期CD中均下调。其他显著变化，如乳腺癌相关蛋白和磺基转移酶2A1的抑制，仅在疾病活动期出现。在UC中，全结肠炎（而非仅左侧结肠炎）与降结肠中主要胆汁酸转运蛋白[多药耐药相关蛋白3（MRP3）、MRP4、多药耐药基因1、有机溶质转运蛋白α/β]和核受体（孕烷X受体、维生素D受体）的表达改变有关。UC全结肠炎导致广泛变化，而CD回肠炎导致肠道胆汁酸转运蛋白表达的选择性变化。早期对肠道胆汁酸转运蛋白进行医学干预可能有助于预防BAM。
