Increased duodenal expression of miR-146a and -155 in pediatric Crohn’s disease

Abstract

The elevated expression of miR-146a and -155 in the inflamed duodenal mucosa of CD patients suggests the role of these miRs in the pathomechanism of inflammatory bowel disease. Anti-inflammatory TGF-β plays an important role in the regulation of the expression of these miRs.

Colonic mucosal and serum expression of microRNAs in canine large intestinal inflammatory bowel disease

“…Chen et al (2013) [51] found that miR-122 targets nucleotide-binding oligomerization domain-2 (NOD2), increasing the anti-inflammatory (IL-4 and IL-10) and decreasing pro-inflammatory cytokines, TNF-α and Interferon-γ (IFN-γ), in Crohn's disease (CD). In another study investigating pediatric CD, there was no difference in the expression of miR-122 in the inflamed mucosa compared to healthy duodenal mucosa of children [50]; however, increased expression of miR-122 was found in the macroscopically normal colonic mucosa of children with CD compared to healthy controls indicating that it may be a marker of reduced intestinal epithelial cell injury [49]. The overexpression of miR-122 in the colonic mucosa of our dogs with IBD, compared to healthy dogs, along with the strongly positive correlation of miR-122 relative expression in the colonic mucosa with the score of epithelial cell injury in the colon, may be attributed to differences in disease pathogenesis, type of infiltrating cells, as well as disease severity and prognosis between canine IBD and pediatric CD.…”

“…miR-122, which is mainly found in the liver, accounts for approximately 70% of all liver miRs, regulates the expression of genes that control cell life cycle [46][47][48], and is considered to be a specific miR for canine hepatobiliary diseases [26,27]. Recent studies have investigated the miR-122 expression in human IBD, including pediatric IBD, and tried to clarify its role in the pathogenesis of disease [49][50][51][52]. Chen et al (2013) [51] found that miR-122 targets nucleotide-binding oligomerization domain-2 (NOD2), increasing the anti-inflammatory (IL-4 and IL-10) and decreasing pro-inflammatory cytokines, TNF-α and Interferon-γ (IFN-γ), in Crohn's disease (CD).…”

MicroRNAs in intestinal barrier function, inflammatory bowel disease and related cancers — their effects and therapeutic potentials

“…Altered microRNA expression profiles were found between inflamed and non-inflamed ascending colon mucosae of CD patients [10 •• ], and microRNAs of the miR-200 family showed enhanced expression in UC dysplastic lesions [11,12]. Patients with pediatric CD showed enhanced duodenal expression of miR-146 , miR-155 and miR-122 [13,14]. MicroRNAs regulated cytokine production in regulatory T cells of UC patients [15], miR-155 targeted Jarid2 transcripts in Th17 cells in an experimental dextran sulfate sodium (DSS)-induced colitis in mouse [16], and increased miR-511-3p expression in mouse macrophages has been linked to intestinal inflammation [17].…”

MicroRNAs in mucosal inflammation

“…These studies revealed specific aberrant miRNA expression patterns for UC that differ from those in CD [102]. Avery recent study in duodenal biopsies from pediatric patients found two miRNAs, miR-146 and miR-155 , with increased expression in inflamed mucosa biopsies [103]. Interestingly, expression levels of both miRNAs in small intestinal epithelial cells or primary duodenal fibroblasts could be reduced by treatment with anti-inflammatory TGF-β, indicating a close association of these miRNAs with pro-inflammatory pathways.…”

“…Several studies also found elevated colonic expression of miR-146a in human IBD patients [67, 102, 103]. MiR-146, representing a key player in controlling the adaptive immune response [104], is also a critical player in the regulation of the T cell function in the intestine.…”