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.

Keywords: EGFR; Intestinal barrier; MicroRNA-122a; Zonulin.