Aberrant Epigenetic Regulation Triggers Intestinal Symptoms in Celiac Disease

Celiac.com 10/11/2016 - Celiac disease is an autoimmune disease in genetically susceptible individuals and is triggered by adverse immune reactions to gluten, a protein found in wheat and other grains.

Researchers led by a research group at Finland's University of Tampere, led by Keijo Viiri, PhD, recently discovered a mechanism that triggers aberrant features in celiac disease and colorectal cancer. Disturbances in this mechanism seem to trigger certain symptoms celiac disease, and possibly in colorectal cancer.

Celiac.com Sponsor (A12):
The research team's recent study offers new details on the pathogenesis of the differentiation defect of the epithelium in the small intestine in celiac disease. When people with celiac disease eat gluten, they suffer intestinal mucosal damage with villus atrophy and crypt hyperplasia. At the cellular level, epithelial cells are less differentiated and hyper-proliferative leading to the malabsorption of nutrients. Researchers discovered that a certain epigenetic mechanism, called Polycomb, governs the homeostasis between the intestinal stem cells in the crypt and the differentiated epithelium in the villi. Polycomb acts by silencing genes epigenetically by methylating histone proteins that are packing the DNA.

"Polycomb is well-known for its function to regulate embryonal development. We discovered that Polycomb is also able to regulate the homeostasis of the small intestine in adults. The regulation of intestinal homeostasis is a tremendous task as the epithelium of the intestine needs to be replenished completely every 4-5 days," says Academy of Finland Postdoctoral Researcher and Principal Investigator Keijo Viiri.

This study demonstrates that in people with celiac disease, dietary gluten triggers excessive activity of Polycomb leading to the aberrant silencing of genes necessary for the differentiation of villus epithelium and to the concomitant differentiation defect in celiac disease. Moreover, the study demonstrates that Polycomb target genes are also dysregulated in colorectal cancer, which suggests that aberrant Polycomb activity is common in intestinal diseases entailing a differentiation defect on the intestinal epithelium.

From a clinical point of view, this work provides new insight into the pathogenesis of the intestinal damage in celiac disease and provides diagnostic markers for the disease.

Since Polycomb regulates only genes imperative for development, this work is also instrumental to further understand the biology of the intestinal homeostasis.

Source:

• Open Original Shared Link