The antimicrobial peptide cathelicidin promotes gastric ulcer healing in rats

Abstract

Cathelicidin, an antimicrobial peptide, has been shown to promote cutaneous wound repair and reaches high levels in the gastric mucosa during infection and inflammation. We therefore investigated whether this peptide contributes to gastric ulcer healing in rats. Ulcer induction increased cathelicidin expression in the gastric mucosa. Further increase in expression of this peptide by local injection of cathelicidin-encoding plasmid promoted ulcer healing by enhancing cell proliferation and angiogenesis. Cathelicidin directly stimulated proliferation of cultured rat gastric epithelial cells (RGM-1), which was abolished by inhibitors of matrix metalloproteinase (MMP), epidermal growth factor (EGFR), or MAPK/ERK kinase (MEK). Cathelicidin also increased EGFR and ERK1/2 phosphorylation via a MMP-dependent mechanism. Knockdown of transforming growth factor α (TGFα), which is a ligand of EGFR, by small interfering RNA completely nullified the mitogenic signals evoked by cathelicidin in RGM-1 cells. These findings suggest that cathelicidin exhibits pro-healing activity in stomachs through TGFα-dependent transactivation of EGFR and its related signaling pathway to induce proliferation of gastric epithelial cells.