Long-term and acute effects of gliadin on small intestine of patients on potentially pathogenic networks in celiac disease.
Celiac disease (CD) is a complex, immune-mediated intolerance to gliadin that develops in genetically susceptible individuals. Although the main driving force of the disease is an aberrant autoimmune response, several other pathogenic mechanisms, many still unidentified, are also involved. In order to describe at a network level the alterations provoked by a gliadin insult on the intestinal mucosa of patients, we compared the expression profiles of biopsies from 9 active and 9 treated patients (long-term effects of gliadin), and of 10 biopsies from gluten-free diet treated patients that were incubated in vitro with or without gliadin (acute effects) and integrated significantly altered transcripts into potentially pathogenic biological processes. Using information on Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology terms represented among the differentially expressed genes, we observed important dysfunction in several complex networks, including those related to cell-cell communication, intracellular signaling, ubiquitin-proteasome system, cell cycle/apoptosis and extracellular matrix. The reconstruction of the role of these biological networks in the development of the intestinal lesion in CD provides a comprehensive picture of key events that contribute to the disease, and could point towards novel functional candidates that might be potential therapeutic targets or responsible for genetic susceptibility.
Castellanos-Rubio
Ainara
A
Hospital de Cruces, Barakaldo, Bizkaia, Spain.
Santin
Izortze
I
Martin-Pagola
Ainhoa
A
Irastorza
Iñaki
I
Castaño
Luis
L
Vitoria
Juan Carlos
JC
Bilbao
Jose Ramon
JR
D002446:Celiac Disease / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D005903:Gliadin / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects*; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects*; D013995:Time
D005903:Gliadin