Gluten affects epithelial differentiation-associated genes in small intestinal mucosa of coeliac patients

• Published in: Clinical and experimental immunology Vol. 150; no. 2; pp. 294 - 305
• Main Authors: Juuti-Uusitalo, K, Mäki, M, Kainulainen, H, Isola, J, Kaukinen, K
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-11-2007; Blackwell Publishing Ltd; Blackwell
• Subjects: Adult; Aged; Analytical, structural and metabolic biochemistry; beta Catenin - genetics; beta Catenin - metabolism; Biological and medical sciences; Biopsy; celiac disease; Celiac Disease - diet therapy; Celiac Disease - genetics; Celiac Disease - immunology; Celiac Disease - pathology; Cell Differentiation - genetics; Cell Differentiation - immunology; coeliac disease; Duodenum - immunology; Duodenum - metabolism; Duodenum - pathology; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - pathology; epithelial differentiation; ErbB Receptors - genetics; ErbB Receptors - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling - methods; Gene Expression Regulation - immunology; genomics; Glutens - immunology; growth factor; Humans; Immunity, Mucosal; immunohistochemistry; immunohistology; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; microarray; Middle Aged; Molecular and cellular biology; Molecular biophysics; Oligonucleotide Array Sequence Analysis; proteomics; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - genetics; Translational Studies; Wiskott-Aldrich Syndrome Protein Family - genetics; Wiskott-Aldrich Syndrome Protein Family - metabolism; Immunohistochemistry; Immunopathology; epithelial differentiation; Digestive system; Genomics; Biochemistry; Biophysics; Cell differentiation; Coeliac disease; Small intestine; immunohistology; Anatomic pathology; microarray; Gene; Intestinal malabsorption; Proteomics; Digestive diseases; Intestinal disease; Genetics; Molecular biology; Differentiation; Genome; Gluten; Growth factor
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2007.03500.x

In coeliac disease gluten induces an immunological reaction in genetically susceptible patients, and influences on epithelial cell proliferation and differentiation in the small-bowel mucosa. Our aim was to find novel genes which operate similarly in epithelial proliferation and differentiation in an epithelial cell differentiation model and in coeliac disease patient small-bowel mucosal biopsy samples. The combination of cDNA microarray data originating from a three-dimensional T84 epithelial cell differentiation model and small-bowel mucosal biopsy samples from untreated and treated coeliac disease patients and healthy controls resulted in 30 genes whose mRNA expression was similarly affected. Nine of 30 were located directly or indirectly in the receptor tyrosine kinase pathway starting from the epithelial growth factor receptor. Removal of gluten from the diet resulted in a reversion in the expression of 29 of the 30 genes in the small-bowel mucosal biopsy samples. Further characterization by blotting and labelling revealed increased epidermal growth factor receptor and beta-catenin protein expression in the small-bowel mucosal epithelium in untreated coeliac disease patients compared to healthy controls and treated coeliac patients. We found 30 genes whose mRNA expression was affected similarly in the epithelial cell differentiation model and in the coeliac disease patient small-bowel mucosal biopsy samples. In particular, those genes involved in the epithelial growth factor-mediated signalling pathways may be involved in epithelial cell differentiation and coeliac disease pathogenesis. The epithelial cell differentiation model is a useful tool for studying gene expression changes in the crypt-villus axis.