Resveratrol enhances MUC2 synthesis via the ANRIL-miR-34a axis to mitigate IBD

Resveratrol (RSV) is a natural polyphenol with strong biological activity that confers a measure of protection against the development of inflammatory bowel disease (IBD), and the long noncoding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) is closely related to inflammation. The present study determined whether resveratrol attenuated IBD by regulating ANRIL and its specific molecular mechanism.

In vivo model of IBD was induced by dextran sulfate sodium (DSS). In total, 60 BALB/c mice were randomly divided into 3 groups (normal control - NC, DSS, RSV), and their weight changes, fecal traits, colon length and tissue hematoxylin-eosin (H&E) were observed. Moreover, human colonic epithelial cells (HCoEpiC) treated with lipopolysaccharide (LPS) were used as cell models of IBD. The tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, IL-10, lncRNA ANRIL, and miR-34a levels were measured by RT-PCR. The expression of mucin 2 (MUC2) and an enzyme associated with MUC2 synthesis, polypeptide N-acetylgalactosaminyltransferase 7 (GALNT7), was measured by RT-PCR and western blot analysis.

Resveratrol treatment mitigated colitis by significantly decreasing the expression of pro-inflammatory cytokines (i.e. TNF-α, IL-1β, IL-6) and miR-34a, and increasing the levels of anti-inflammatory cytokine (i.e. IL-10), MUC2, GLNAT7, and lncRNA ANRIL in mice and HCoEpiC (all P<0.05). The elevated synthesis of MUC2 could be attributed to the ANRIL-miR-34a axis.

Resveratrol attenuates IBD by promoting MUC2 synthesis via the ANRIL-miR-34a axis.