Adrenomedullin alleviates mucosal injury in experimental colitis and increases claudin‐4 expression in the colonic epithelium

Adrenomedullin (AM) is a peptide with pleiotropic physiological functions that attenuates intestinal mucosal inflammation. However, the mechanism underpinning mucosal protection by AM is not fully understood, and its effect on intestinal epithelial cells remains unclear. Here, we investigated the effects of AM on junctional molecules in primary‐cultured murine intestinal epithelial cells and discovered that AM upregulates claudin‐4 expression. In a mouse model of dextran sulfate sodium‐induced colitis, AM administration also enhanced claudin‐4 expression and accelerated mucosal regeneration. Furthermore, AM reversed TNFα‐mediated downregulation of claudin‐4 and loss of cell–cell adhesion of the HCT116 human intestinal epithelial cell line in vitro. These results indicate that AM may enhance intestinal epithelial integrity by upregulating claudin‐4 expression. Adrenomedullin (AM) is a bioactive peptide with pleiotropic functions. We showed that AM promotes the regeneration of injured intestinal epithelium via the upregulation of claudin‐4 in murine DSS‐induced colitis model. Moreover, AM ameliorated the decreased expression of claudin‐4 caused by TNFα treatment in human colonic epithelial cells. These results suggest that AM may enhance intestinal epithelial integrity by upregulating claudin‐4 expression.