RNA sequencing shows transcriptomic changes in rectosigmoid mucosa in patients with irritable bowel syndrome-diarrhea: a pilot case-control study

被引：55
作者：
Camilleri, Michael [1 ]
Carlson, Paula [1 ]
Acosta, Andres [1 ]
Busciglio, Irene [1 ]
Nair, Asha A. [2 ]
Gibbons, Simon J. [1 ]
Farrugia, Gianrico [1 ]
Klee, Eric W. [2 ]
机构：
[1] Mayo Clin, Rochester, MN 55905 USA
[2] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA
来源：
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2014年 / 306卷 / 12期
关键词：
neurotransmitters; ion channels; cytokines; barrier; mucosal repair; SEROTONIN TRANSPORTER; EXPRESSION; GENE; ASSOCIATION; TRANSIT; COLON; INTESTINE; DISEASE; TNFSF15; POLYMORPHISMS;
D O I：
10.1152/ajpgi.00068.2014
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
Our aim was to conduct a pilot case-control study of RNA expression profile using RNA sequencing of rectosigmoid mucosa of nine females with -diarrhea-predominant irritable bowel syndrome (IBS-D) with accelerated colonic transit and nine female healthy controls. Mucosal total RNA was isolated and purified, and next-generation pair-end sequencing was performed using Illumina TruSeq. Analysis was carried out using a targeted approach toward 12 genes previously associated with IBS and a hypothesis-generating approach. Of the 12 targeted genes tested, patients with IBS-D had decreased mRNA expression of TNFSF15 (fold change controls to IBS-D: 1.53, P = 0.01). Overall, up-and downregulated mRNA expressions of 21 genes (P = 10(-5) to 10(-8); P values with false detection rates are shown) were potentially relevant to IBS-D including the following: neurotransmitters [P2RY4 (P = 0.001), vasoactive intestinal peptide (VIP, P = 0.02)]; cytokines [CCL20 (P = 0.019)]; immune function [C4BPA complement cascade (P = 0.0187)]; interferon-related [IFIT3 (P = 0.016)]; mucosal repair and cell adhesion [trefoil protein (TFF1, P = 0.012)], retinol binding protein [RBP2 (P = 0.017)]; fibronectin (FN1, P = 0.009); and ion channel functions [guanylate cyclase (GUCA2B, P = 0.017), PDZ domain-containing protein 3 (PDZD3, P = 0.029)]. Ten genes associated with functions related to pathobiology of IBS-D were validated by RT-PCR. There was significant correlation in fold changes of the selected genes (Rs = 0.73, P = 0.013). Up-or downregulation of P2RY4, GUC2AB, RBP2, FNI, and C4BPA genes were confirmed on RT-PCR, which also revealed upregulation of farnesoid X receptor (FXR) and apical sodium-coupled bile acid transporter (IBAT/ASBT). RNA-Seq and RT-PCR analysis of rectosigmoid mucosa in IBS-D show transcriptome changes that provide the rationale for validation studies to explore the role of mucosal factors in the pathobiology of IBS-D.
引用
收藏
页码：C1089 / C1098
页数：10
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