miR-122 targets NOD2 to decrease intestinal epithelial cell injury in Crohn’s disease

• Published in: Biochemical and biophysical research communications Vol. 438; no. 1; pp. 133 - 139
• Main Authors: Chen, Yu, Wang, Chengxiao, Liu, Ying, Tang, Liwei, Zheng, Mingxia, Xu, Chundi, Song, Jian, Meng, Xiaochun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16-08-2013
• Subjects: 60 APPLIED LIFE SCIENCES; APOPTOSIS; Binding Sites; Crohn Disease - metabolism; Crohn Disease - pathology; Crohn’s disease (CD); Down-Regulation; Epithelial Cells - metabolism; Epithelial Cells - pathology; GENES; HT29 Cells; Humans; IBD; INFLAMMATION; INJURIES; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; LYMPHOKINES; MicroRNAs - metabolism; miR-122; NOD2; Nod2 Signaling Adaptor Protein - metabolism; NUCLEOTIDES; Protein Binding; IBD; NOD2; Crohn’s disease (CD); miR-122
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.07.040

•NOD2 is a target gene of miR-122.•miR-122 inhibits LPS-induced apoptosis by suppressing NOD2 in HT-29 cells.•miR-122 reduces the expression of pro-inflammatory cytokines (TNF-α and IFN-γ).•miR-122 promotes the release of anti-inflammatory cytokines (IL-4 and IL-10).•NF-κB signaling pathway is involved in inflammatory response induced by LPS.
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.