The cationic host defense peptide rCRAMP promotes gastric ulcer healing in rats

J Pharmacol Exp Ther. 2006 Aug;318(2):547-54. doi: 10.1124/jpet.106.102467. Epub 2006 May 2.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid
  • Actins / genetics
  • Actins / physiology
  • Animals
  • Anti-Ulcer Agents*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Blotting, Western
  • Cell Proliferation
  • Cell Survival / genetics
  • Cells, Cultured
  • Epithelial Cells / physiology
  • ErbB Receptors / metabolism
  • Gastric Mucosa / cytology
  • Gastric Mucosa / drug effects
  • Genetic Therapy*
  • Immunohistochemistry
  • Immunoprecipitation
  • Male
  • Mitosis / drug effects
  • Neovascularization, Physiologic / genetics
  • Neovascularization, Physiologic / physiology
  • Phosphorylation
  • Plasmids / genetics
  • RNA, Small Interfering
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / therapy*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Actins
  • Anti-Ulcer Agents
  • Antimicrobial Cationic Peptides
  • RNA, Small Interfering
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • ropocamptide
  • Egfr protein, rat
  • ErbB Receptors
  • Acetic Acid