Changes in mRNA Expression Levels of Solute Carrier Transporters in Inflammatory Bowel Disease Patients

溶质载体族 运输机 炎症性肠病 基因表达 生物 内分泌学 炎症 信使核糖核酸 内科学 化学 医学 生物化学 基因 疾病
作者
Kacper A. Wojtal,Jyrki J. Eloranta,Petr Hrúz,Heike Gutmann,Jürgen Drewe,Alex Staumann,Christoph Beglinger,Michael Fried,Gerd A. Kullak‐Ublick,Stephan R. Vavricka
出处
期刊:Drug Metabolism and Disposition [American Society for Pharmacology & Experimental Therapeutics]
卷期号:37 (9): 1871-1877 被引量:142
标识
DOI:10.1124/dmd.109.027367
摘要

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 Crohn9s 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.

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