Colonic mucosal gene expression and genotype in irritable bowel syndrome patients with normal or elevated fecal bile acid excretion.
The mucosal gene expression in rectosigmoid mucosa (RSM) in irritable bowel syndrome with diarrhea (IBS-D) is unknown. Our objectives were, first, to study mRNA expression [by RT(2) PCR of 19 genes pertaining to tight junctions, immune activation, intestinal ion transport and bile acid (BA) homeostasis] in RSM in IBS-D patients (n = 47) and healthy controls (n = 17) and study expression of a selected protein (PDZD3) in 10 IBS-D patients and 4 healthy controls; second, to assess RSM mRNA expression according to genotype and fecal BA excretion (high ≥ 2,337 μmol/48 h); and third, to determine whether genotype or mucosal mRNA expression is associated with colonic transit or BA parameters. Fold changes were corrected for false detection rate for 19 genes studied (P < 0.00263). In RSM in IBS-D patients compared with controls, mRNA expression of GUC2AB, PDZD3, and PR2Y4 was increased, whereas CLDN1 and FN1 were decreased. One immune-related gene was upregulated (C4BP4) and one downregulated (CCL20). There was increased expression of a selected ion transport protein (PDZD3) on immunohistochemistry and Western blot in IBS-D compared with controls (P = 0.02). There were no significant differences in mucosal mRNA in 20 IBS-D patients with high compared with 27 IBS-D patients with normal BA excretion. GPBAR1 (P < 0.05) was associated with colonic transit. We concluded that mucosal ion transport mRNA (for several genes and PDZD3 protein) is upregulated and barrier protein mRNA downregulated in IBS-D compared with healthy controls, independent of genotype. There are no differences in gene expression in IBS-D with high compared with normal fecal BA excretion.
Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota camilleri.michael@mayo.edu.
Michael
M
Camilleri
Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota.
Paula
P
Carlson
Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota.
Andres
A
Acosta
Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota.
Irene
I
Busciglio
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D001647:Bile Acids and Salts / Q000378:metabolism*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules; D003106:Colon / Q000378:metabolism* / Q000503:physiopathology; D005243:Feces / Q000737:chemistry; D005260:Female; D005772:Gastrointestinal Transit; D005786:Gene Expression Regulation; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D043183:Irritable Bowel Syndrome / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D010539:Permeability; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D001647:Bile Acids and Salts; D015815:Cell Adhesion Molecules; D005819:Genetic Markers; D009363:Neoplasm Proteins; C423943:PDZD2 protein, human; D012333:RNA, Messenger
GUCA2B; PDZD3; barrier; cytokines; immune; ion channels; neurotransmitters; secretion