4th Annual BMRP Investigator Meeting - Abstract
Involvement of the Apelin in Colonic Epithelial Proliferation
Guiyun Wang1, Song Han1, Ella Englander1,2, and George H. Greeley, Jr.1,a
1Department of Surgery, The University of Texas Medical Branch (Galveston, Texas, U.S.A.); 2Shriners Hospitals for Children (Galveston, Texas, U.S.A.)
Apelin is the endogenous ligand for the APJ receptor. Apelin and APJ are expressed widely in the body, including the gastrointestinal tract. Our laboratory has shown that colonic apelin mRNA and peptide levels are increased in rodent models of experimental colitis and that colonic apelin immunostaining is increased in IBD patients. In mice and rats given dextran sodium sulfate (DSS) to induce colitis, colonic apelin expression and peptide levels are increased during the inflammatory reaction in response to DSS drinking water as well as during the tissue repair phase that ensues after DSS withdrawal suggesting that apelin plays multiple roles during the different stages of colitis.
The aim of these studies was to examine the effect of exogenous apelin on colonic epithelial proliferation in mice. The effect of apelin (50 µg, 3x/day for three days, SC) on colonic epithelial proliferation was assessed in mice by giving BrdU (290 mg/kg) 90 min before sacrifice. BrdU incorporation was examined by immunohistochemical (IHC) staining. Results show that apelin administration decreased the colonic proliferation rate by 50% (control BrdU cells: 149 ± 23 vs apelin treated BrdU cells: 67 ± 16/field; N=5 mice/group, P<0.05).
These findings when considered with the increased apelin production during colitis in rodents with experimental colitis and in humans with inflammatory bowel disease (IBD) reflect an adaptive response to modulate epithelial restitution and mucosal repair. Additionally, these findings suggest that the increased apelin expression during intestinal inflammation contributes to the refractory nature of the poorly healing intestinal epithelium during colitis in IBD patients.
aPrincipal Investigator