Enterocyte proliferation and signaling are constitutively altered in celiac disease.

Abstract

Celiac disease (CD) occurs frequently, and is caused by ingestion of prolamins from cereals in subjects with a genetic predisposition. The small intestinal damage depends on an intestinal stress/innate immune response to certain gliadin peptides (e.g., A-gliadin P31-43) in association with an adaptive immune response to other gliadin peptides (e.g., A-gliadin P57-68). Gliadin and peptide P31-43 affect epithelial growth factor receptor (EGFR) signaling and CD enterocyte proliferation. The reason why the stress/innate immune and proliferative responses to certain gliadin peptides are present in CD and not in control intestine is so far unknown. The aim of this work is to investigate if, in CD, a constitutive alteration of enterocyte proliferation and signaling exists that may represent a predisposing condition to the damaging effects of gliadin. Immunofluorescence and immunohistochemistry were used to study signaling in CD fibroblasts and intestinal biopsies. Western blot (WB) analysis, immunoprecipitation, and quantitative PCR were also used. We found in CD enterocytes enhancement of both proliferation and Epidermal Growth Factor Receptor (EGFR)/ligand system. In CD enterocytes and fibroblasts we found increase of the phosphorylated downstream signaling molecule Extracellular Signal Regulated Kinase (ERK); block of the ERK activation normalizes enterocytes proliferation in CD mucosa. In conclusion the same pathway, which gliadin and gliadin peptide P31-43 can interfere with, is constitutively altered in CD cells. This observation potentially explains the specificity of the damaging effects of certain gliadin peptides on CD intestine.

• Authors: Merlin Nanayakkara, Giuliana Lania, Mariantonia Maglio, Roberta Kosova, Marco Sarno, Alessandra Gaito, Valentina Discepolo, Riccardo Troncone, Salvatore Auricchio, Renata Auricchio, Maria Vittoria Barone
• Journal: PloS one (PLoS One) Vol. 8 Issue 10 Pg. e76006 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24204586 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epidermal Growth Factor
• ErbB Receptors
• Extracellular Signal-Regulated MAP Kinases

Topics

• Adolescent
• Biopsy
• Celiac Disease (genetics, metabolism, pathology)
• Cell Proliferation
• Child
• Child, Preschool
• Enterocytes (metabolism, pathology)
• Epidermal Growth Factor (genetics, metabolism)
• ErbB Receptors (metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Humans
• Infant
• Intestinal Mucosa (metabolism, pathology)
• Phosphorylation
• Signal Transduction