MicroRNA-122a Regulates Zonulin by Targeting EGFR in Intestinal Epithelial Dysfunction

Abstract

Background/Aims: This study aimed to investigate the role of microRNA (miR)-122a in regulating zonulin during the modulation of intestinal barrier. Methods: Zonulin proteins and their target gene expression were analyzed in miR-122a-overexpressing cell lines and in the target gene of epidermal growth factor receptor (EGFR). An mmu-miR-122a intestinal epithelial conditional transgenic (miR-122a-TG) mouse model was established to investigate EGFR and zonulin expression. MiR-122a was also detected in the clinical specimens of inflammatory bowel disease. Results: EGFR was identified as a target gene of miR-122a. The expression level of miR-122a was positively correlated with that of zonulin. The expression level of zonulin was significantly increased, whereas the expression level of EGFR was significantly decreased in the miR-122a-TG mice and in the corresponding primary epithelial culture (P < 0.05). These results were consistent with the data of the clinical specimens. Conclusions: miR-122a could be a positive factor of zonulin by targeting EGFR, which increased the intestinal epithelial permeability in vivo and in vitro.

MiRNAs and inflammatory bowel disease: An interesting new story

“…MiR-122a also increases zonulin levels by decreasing the epidermal growth factor-receptor (EGFR) level and targeting the EGFR signaling pathways (A. Zhang, Wang, et al, 2017;B. Zhang, Tian, et al, 2017).…”

“…MiR-191a and miR-212 ZO-1 Weaken tight junctions Tang et al (2015) and L. Wang et al (2017) MiR-675 Cadherin E and ZO-1 Destructs tight junctions Zou et al (2016) MiR-874 Aquaporin 3 Weakens the intestinal barrier Su et al (2016), W. Zhang et al (2011), X. Zhi et al (2014 MiR-122a Zonulin Decreases EGFR level and targeting EGFR signaling pathways Increases the intestine permeability A. Zhang, Wang, et al (2017) andB. Zhang, Tian, et al (2017) MiR-21 PTEN/PI3K/Akt signaling Exerts destructive effect on intestinal barrier Regulates permeability of tight junctions C. Zhang, Xi, et al (2015), L. Zhang, Ke, et al (2015), and L. Zhang, Shen, et al (2015) MiR Note.…”

Protective Effects of Let-7b on the Expression of Occludin by Targeting P38 MAPK in Preventing Intestinal Barrier Dysfunction

“…Hundreds of miRNAs have been described in humans, and an estimate of no less than 1000 miRNAs have been encoded by the human genome [4]. MiRNAs are involved in the regulation of gene expression in numerous critical biological processes [5], such as development, differentiation, apoptosis, and proliferation [6]. Upon structural analysis, the pre-translational level governance of miRNAs has been estimated to affect half of the human transcripts, whereas functional studies indicated that miRNAs might participate in almost every cellular process investigated to date [7].…”

Fecal MicroRNAs as Potential Biomarkers for Screening and Diagnosis of Intestinal Diseases

“… Cichon et al (2014) reported that the intestinal barrier function is impaired in a typical Dicer1-deficient mouse model (i.e., absence of mmu-miR-192), resulting in spontaneous intestinal inflammation. Of note, miRNAs, such as miR-122a and miR-21, target negative regulators of immune response to promote inflammation ( Ye et al, 2011 ; Zhang et al, 2015 , 2017 ). Several investigations reveal that inflammatory cytokines such as tumor necrosis factor (TNF)-α and interferon gamma (IFNγ) may increase greatly the expression of miRNAs in enterocytes, cultured cells, and intestinal tissues ( Ye et al, 2011 ; Haines et al, 2016 ).…”