Wojtal Kacper A, Eloranta Jyrki J, Hruz Petr, Gutmann Heike, Drewe Jürgen, Staumann Alex, Beglinger Christoph, Fried Michael, Kullak-Ublick Gerd A, Vavricka Stephan R
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
Drug Metab Dispos. 2009 Sep;37(9):1871-7. doi: 10.1124/dmd.109.027367. Epub 2009 Jun 1.
Inflammatory bowel disease (IBD) is an inflammatory condition that affects the gastrointestinal tract. The solute carrier (SLC) superfamily of transporters comprise proteins involved in the uptake of drugs, hormones, and other biologically active compounds. The purpose of this study was to determine the mRNA expression levels of 15 solute carrier transporters in two regions of the intestine in IBD patients. Endoscopic biopsy specimens were taken from two locations (terminal ileum and colon) for histological examination and RNA extraction. We quantitatively measured the mRNA expression of 15 SLC transporters in 107 IBD patients (53 with Crohn's disease and 54 with ulcerative colitis) and 23 control subjects. mRNA expression was evaluated using the quantitative reverse transcription-polymerase chain reaction technique. We observed that in the ileum of IBD patients, mRNA levels for serotonin transporter, equilibrative nucleoside transporter (ENT) 1, ENT2, and organic anion-transporting polypeptide (OATP) 2B1 were significantly elevated, whereas levels for apical sodium-dependent bile acid transporter (ASBT) and organic zwitterion/cation transporter (OCTN) 2 were significantly lower. In colon, mRNA levels for ENT1, ENT2, concentrative nucleoside transporter (CNT) 2, OATP2B1, and OATP4A1 were significantly higher, whereas mRNA levels for OCTN2 were significantly decreased. In inflamed colon of IBD patients the mRNA expression levels of ENT1, ENT2, CNT2, OATP2B1, OATP4A1, and peptide transporter 1 were significantly higher. We conclude that intestinal SLC mRNA levels are dysregulated in IBD patients, which may be linked to the inflammation of the tissue and provides an indication about the role of inflammatory signaling in regulation of SLC expression.
炎症性肠病(IBD)是一种影响胃肠道的炎症性疾病。溶质载体(SLC)转运蛋白超家族包括参与药物、激素和其他生物活性化合物摄取的蛋白质。本研究的目的是确定IBD患者肠道两个区域中15种溶质载体转运蛋白的mRNA表达水平。从两个部位(回肠末端和结肠)采集内镜活检标本进行组织学检查和RNA提取。我们定量测量了107例IBD患者(53例克罗恩病患者和54例溃疡性结肠炎患者)和23名对照受试者中15种SLC转运蛋白的mRNA表达。使用定量逆转录-聚合酶链反应技术评估mRNA表达。我们观察到,在IBD患者的回肠中,血清素转运蛋白、平衡核苷转运蛋白(ENT)1、ENT2和有机阴离子转运多肽(OATP)2B1的mRNA水平显著升高,而顶端钠依赖性胆汁酸转运蛋白(ASBT)和有机两性离子/阳离子转运蛋白(OCTN)2的水平显著降低。在结肠中,ENT1、ENT2、浓缩核苷转运蛋白(CNT)2、OATP2B1和OATP4A1的mRNA水平显著升高,而OCTN2的mRNA水平显著降低。在IBD患者发炎的结肠中,ENT1、ENT2、CNT2、OATP2B1、OATP4A1和肽转运蛋白1的mRNA表达水平显著更高。我们得出结论,IBD患者肠道SLC mRNA水平失调,这可能与组织炎症有关,并提示炎症信号在SLC表达调节中的作用。