The miR-7/EGFR axis controls the epithelial cell immunomodulation and regeneration and orchestrates the pathology in inflammatory bowel disease

The epithelial immunomodulation and regeneration are fundamental and intrinsic critical events against inflammatory bowel disease (IBD). MiR-7 is well implicated as a promising regulator in the pathologies of inflammatory diseases. Herein, we investigate the role of miR-7 in intestinal epithelial cells (IECs) in IBD. We found that miR-7 expression, which is mainly derived from miR-7a-1 operated by transcriptional factor C/EBPα, is increased in IECs from IBD model and Crohn's disease patients. MiR-7 controls the immunomodulation and regeneration of epithelial cells through EGFR/NF-κB/ERK/AKT signaling pathways. Epithelial cell-specific miR-7 silencing alleviates the pathology of IBD model. Therefore, our data reveal the unknown role of miR-7/EGFR axis in IEC immunomodulation and regeneration in IBD and might provide a clue for the development of miRNA-based therapeutic strategy applications in colonic diseases. [Display omitted] •The expression of miR-7, operated by transcriptional factor C/EBPα, is increased in IECs in IBD.•MiR-7 controls the immunomodulation and regeneration of IECs through EGFR signaling pathways.•Epithelial cell-specific miR-7 silencing alleviates the pathology of Colitis model. The epithelial immunomodulation and regeneration are intrinsic critical events against inflammatory bowel disease (IBD). MiR-7 is well documented as a promising regulator in the development of various diseases including inflammatory diseases. This study aimed to assess the effect of miR-7 in intestinal epithelial cells (IECs) in IBD. MiR-7def mice were given dextran sulfate sodium (DSS) to induce enteritis model. The infiltration of inflammatory cells was measured by FCM and immunofluorescence assay. 5′deletion assay and EMSA assays were performed to study the regulatory mechanism of miR-7 expression in IECs. The inflammatory signals and the targets of miR-7 were analyzed by RNA-seq and FISH assay. IECs were isolated from miR-7def, miR-7oe and WT mice to identify the immunomodulation and regeneration capacity. IEC-specific miR-7 silencing expression vector was designed and administered by the tail vein into murine DSS-induced enteritis model to evaluate the pathological lesions of IBD. We found miR-7 deficiency improved the pathological lesions of DSS-induced murine enteritis model, accompanied by elevated proliferation and enhanced transduction of NF-κB/AKT/ERK signals in colonic IECs, as well as decreased local infiltration of inflammatory cells. MiR-7 was dom