miR-16 and miR-125b are involved in barrier function dysregulation through the modulation of claudin-2 and cingulin expression in the jejunum in IBS with diarrhoea

摘要: Objective Micro-RNAs (miRNAs) play a crucial role in controlling intestinal epithelial barrier function partly by modulating the expression of tight junction (TJ) proteins. We have previously shown differential messenger RNA (mRNA) correlated with ultrastructural abnormalities patients diarrhoea-predominant IBS (IBS-D). However, participation miRNAs these mRNA-associated findings remains to be established. Our aims were (1) identify differentially expressed small bowel mucosa IBS-D and (2) explore putative target genes specifically involved that are controlled specific dysregulated miRNAs. Design Healthy controls meeting Rome III criteria studied. Intestinal tissue samples analysed potential candidates by: (a) miRNA-mRNA profiling; (b) pairing analysis assess co-expression profile pairs; (c) pathway upstream regulator identification; (d) miRNA mRNA validation. Candidate pairs functionally assessed cells. Results showed distinct profiles compared healthy controls. TJ signalling was associated transcriptional profile. Further validation selected consistent upregulation 75% function. Bioinformatic binding sites identified hsa-miR-125b-5p hsa-miR-16 as regulating CGN (cingulin) CLDN2 (claudin-2), respectively. Consistently, protein upregulated IBS-D, while respective targeting downregulated. In addition, dysfunction, perceived stress depression number mast cells their Conclusions Modulation involves both post-transcriptional mechanisms. These molecular mechanisms include master regulators proteins major clinical symptoms.