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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on May 2, 2006; DOI: 10.1124/jpet.106.102467

0022-3565/06/3182-547-554$20.00
JPET 318:547-554, 2006
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GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

The Cationic Host Defense Peptide rCRAMP Promotes Gastric Ulcer Healing in Rats

Ying H. Yang, William K. K. Wu, Emily K. K. Tai, Helen P. S. Wong, Emily K. Y. Lam, Wallace H. L. So, Vivian Y. Shin, and Chi H. Cho

Department of Biology, Hai Nam Normal University, Hai Kou, China (Y.H.Y.); and Department of Pharmacology (Y.H.Y., W.K.K.W., E.K.K.T., H.P.S.W., E.K.Y.L., W.H.L.S., V.Y.S., C.H.C.) and Research Center of Infection and Immunology (C.H.C.), Faculty of Medicine, The University of Hong Kong, Hong Kong, China

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} (TGF{alpha}), 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 TGF{alpha}-dependent transactivation of EGFR and its related signaling pathway to induce proliferation of gastric epithelial cells.

Received February 6, 2006; accepted April 28, 2006.

Address correspondence to: Dr. Chi H. Cho, Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong, China. E-mail: chcho{at}hkusua.hku.hk




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E. K. K. Tai, W. K. K. Wu, H. P. S. Wong, E. K. Y. Lam, L. Yu, and C. H. Cho
A New Role for Cathelicidin in Ulcerative Colitis in Mice
Experimental Biology and Medicine, June 1, 2007; 232(6): 799 - 808.
[Abstract] [Full Text] [PDF]


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