miRNA-regulated gene expression differs in celiac disease patients according to the age of presentation

Abstract

Celiac disease is an intestinal disease which shows different symptoms and clinical manifestations among pediatric and adult patients. These variations could be imputable to age-related changes in gut architecture and intestinal immune system, which could be characterized by gene expression differences possibly regulated by miRNAs. We analyzed a panel of miRNAs and their target genes in duodenal biopsies of Marsh 3AB and 3C pediatric celiac patients, compared to controls. Moreover, to assess variation of expression in plasma samples, we evaluated circulating miRNA levels in controls and patients at diagnosis or on gluten-free diet. We detected a decreased miR-192-5p expression in celiac patients, but no variations in NOD2 and CXCL2, targets previously identified in adults. Conversely, we detected a significant increase in mRNA and protein levels of another target, MAD2L1, protein related to cell cycle control. miR-31-5p and miR-338-3p were down-regulated and their respective targets, FOXP3 and RUNX1, involved in Treg function, resulted up-regulated in celiac patients. Finally, we detected, in celiac patients, an increased expression of miR-21-5p, possibly caused by a regulatory loop with its putative target STAT3, which showed an increased activation in Marsh 3C patients. The analysis of plasma revealed a trend similar to that observed in biopsies, but in presence of gluten-free diet we could not detect circulating miRNAs values comparable to controls. miRNAs and their gene targets showed an altered expression in duodenal mucosa and plasma of celiac disease pediatric patients, and these alterations could be different from adult ones.

Circulating microRNAs as potential non-invasive biomarkers in pediatric patients with celiac disease

“…In addition, circulating miR-31-5p in untreated CD patients displayed a significantly decline compared to controls. Moreover, there is no statistically significant difference in miRNA levels between controls and CD patients on a gluten-free diet (2). In a study performed by Magni et al (2014) in the duodenum of adult CD patients, the significantly decreased expression of miR-192-5p, miR-31-5p, miR-338-3p, and miR-197 were demonstrated as compared with controls (5).…”

“…After that, they evaluated the circulating miRNA patterns in untreated CD patients or on a gluten-free diet compared to controls. They found that miR-31-5p and miR-338-3p were underexpressed in the duodenum samples of CD patients (2). In addition, circulating miR-31-5p in untreated CD patients displayed a significantly decline compared to controls.…”

“…Celiac disease (CD) is an autoimmune disease affecting the small intestine with a prevalence of 1 in 100 to 1 in 200 subjects, particularly children (1)(2)(3). This enteropathy is triggered by the interaction of environmental and genetic factors (3,4).…”

“…This enteropathy is triggered by the interaction of environmental and genetic factors (3,4). CD is characterized by an immunological reaction against the TG2 (transglutaminase type 2) enzyme triggered by the ingestion of gluten peptides from wheat and related cereals in genetically predisposed individuals (2,5,6). This autoimmune reaction induces a duodenal damage characterized by villous atrophy, intraepithelial lymphocytosis, infiltration of inflammatory cells in the lamina propria and crypt hyperplasia (7,8).…”

miR-146b antagomir–treated human Tregs acquire increased GVHD inhibitory potency

“…13,14 Multiple mechanisms have been implicated in tTreg development and suppressive function, including more recently miRNA's effects on posttranscriptional gene regulation. [15][16][17][18] The miR-146 family includes 2 main members, miR-146a and miR-146b, which are both highly expressed and play important roles in cell proliferation and function in diverse cell types, including T and B cells. Studies of breast cancer cells have shown a Foxp3-dependant increase in the expression of miR-146b and, to a lesser extent, miR-146a, 19 which results in reduced breast cancer cell proliferation and enhanced apoptosis via negative regulation of nuclear factor kB (NF-kB).…”