title: miR-122 targets NOD2 to decrease intestinal epithelial cell injury in Crohn's disease.
abstract: Crohn's disease (CD) is one of the two major types of inflammatory bowel disease (IBD) thought to be caused by genetic and environmental factors. Recently, miR-122 was found to be deregulated in association with CD progression. However, the underlying molecular mechanisms remain unclear. In the present study, the gene nucleotide-binding oligomerization domain 2 (NOD2/CARD15), which is strongly associated with susceptibility to CD, was identified as a functional target of miR-122. MiR-122 inhibited LPS-induced apoptosis by suppressing NOD2 in HT-29 cells. NOD2 interaction with LPS initiates signal transduction mechanisms resulting in the activation of nuclear factor κB (NF-κB) and the stimulation of downstream pro-inflammatory events. The activation of NF-κB was inhibited in LPS-stimulated HT-29 cells pretreated with miR-122 precursor or NOD2 shRNA. The expression of the pro-inflammatory cytokines TNF-α and IFN-γ was significantly decreased, whereas therelease of the anti-inflammatory cytokines IL-4 and IL-10 was increased in LPS-stimulated HT-29 cells pretreated with miR-122 precursor, NOD2 shRNA or the NF-κB inhibitor QNZ. Taken together, these results indicate that miR-122 and its target gene NOD2 may play an important role in the injury of intestinal epithelial cells induced by LPS.
authors.affiliation: Department of Pediatrics, Jiangwan Hospital of Shanghai, Shanghai 200434, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Chengxiao
authors.initials: C
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Liwei
authors.initials: L
authors.lastname: Tang
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zheng
authors.forename: Chundi
authors.initials: C
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Meng
mesh_terms: D001665:Binding Sites; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D011485:Protein Binding
chemical_list: C531907:MIRN122 microRNA, human; D035683:MicroRNAs; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein
keywords: Crohn’s disease (CD); IBD; NOD2; miR-122