TY - JOUR
T1 - Differential mRNA Expression in Ileal Mucosal Biopsies of Patients with Diarrhea- or Constipation-Predominant Irritable Bowel Syndrome
AU - Wang, Xiao Jing
AU - Carlson, Paula
AU - Chedid, Victor
AU - Maselli, Daniel B.
AU - Taylor, Ann L.
AU - McKinzie, Sanna
AU - Camilleri, Michael
N1 - Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/4/12
Y1 - 2021/4/12
N2 - INTRODUCTION:Previous studies in patients with irritable bowel syndrome (IBS) showed immune activation, secretion, and barrier dysfunction in duodenal, jejunal, or colorectal mucosa. This study aimed to measure ileal mucosal expression of genes and proteins associated with mucosal functions.METHODS:We measured by reverse transcription polymerase chain reaction messenger RNA (mRNA) expression of 78 genes (reflecting tight junction proteins, chemokines, innate immunity, ion channels, and transmitters) and 5 proteins (barrier, bile acid receptor, and ion exchanger) in terminal ileal mucosa from 11 patients with IBS-diarrhea (IBS-D), 17 patients with IBS-constipation (IBS-C), and 14 healthy controls. Fold changes in mRNA were calculated using 2(-Δ, ΔCT)formula. Group differences were measured using analysis of variance. Protein ratios relative to healthy controls were based on Western blot analysis. Nominal P values (P < 0.05) are reported.RESULTS:In ileal mucosal biopsies, significant differences of mRNA expression in IBS-D relative to IBS-C were upregulation of barrier proteins (TJP1, FN1, CLDN1, and CLDN12), repair function (TFF1), and cellular functions. In ileal mucosal biopsies, mRNA expression in IBS-C relative to healthy controls was reduced GPBAR1 receptor, myosin light chain kinase (MYLK in barrier function), and innate immunity (TLR3), but increased mRNA expression of cadherin cell adhesion mechanisms (CTNNB1) and transport genes SLC9A1 (Na-H exchanger [NHE1]) and INADL (indirect effect on ion transport).DISCUSSION:These data support a role of ileal mucosal dysfunction in IBS, including barrier dysfunction in IBS-D and alterations in absorption/secretion mechanisms in IBS-C.
AB - INTRODUCTION:Previous studies in patients with irritable bowel syndrome (IBS) showed immune activation, secretion, and barrier dysfunction in duodenal, jejunal, or colorectal mucosa. This study aimed to measure ileal mucosal expression of genes and proteins associated with mucosal functions.METHODS:We measured by reverse transcription polymerase chain reaction messenger RNA (mRNA) expression of 78 genes (reflecting tight junction proteins, chemokines, innate immunity, ion channels, and transmitters) and 5 proteins (barrier, bile acid receptor, and ion exchanger) in terminal ileal mucosa from 11 patients with IBS-diarrhea (IBS-D), 17 patients with IBS-constipation (IBS-C), and 14 healthy controls. Fold changes in mRNA were calculated using 2(-Δ, ΔCT)formula. Group differences were measured using analysis of variance. Protein ratios relative to healthy controls were based on Western blot analysis. Nominal P values (P < 0.05) are reported.RESULTS:In ileal mucosal biopsies, significant differences of mRNA expression in IBS-D relative to IBS-C were upregulation of barrier proteins (TJP1, FN1, CLDN1, and CLDN12), repair function (TFF1), and cellular functions. In ileal mucosal biopsies, mRNA expression in IBS-C relative to healthy controls was reduced GPBAR1 receptor, myosin light chain kinase (MYLK in barrier function), and innate immunity (TLR3), but increased mRNA expression of cadherin cell adhesion mechanisms (CTNNB1) and transport genes SLC9A1 (Na-H exchanger [NHE1]) and INADL (indirect effect on ion transport).DISCUSSION:These data support a role of ileal mucosal dysfunction in IBS, including barrier dysfunction in IBS-D and alterations in absorption/secretion mechanisms in IBS-C.
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U2 - 10.14309/ctg.0000000000000329
DO - 10.14309/ctg.0000000000000329
M3 - Article
C2 - 33843785
AN - SCOPUS:85104212212
SN - 2155-384X
VL - 12
SP - E00329
JO - Clinical and translational gastroenterology
JF - Clinical and translational gastroenterology
IS - 4
ER -