Scientific Abstract

Proposal No.   IBD-0118
Principal Investigator:  George H. Greeley, Jr., Ph.D.
Applicant Organization:  The University of Texas Medical Branch (Galveston, U.S.A.)
Project Title:  Protective and repair action of apelin, a new enteric protein, on the intestinal mucosa in experimental colitis
Period of Award:  June 1, 2004 - September 30, 2006

Intestinal-mucosal injury is a hallmark of inflammatory bowel disease (IBD).  The goals of this project are to investigate the influence of IBD in humans and experimental colitis in animals on expression of apelin and its receptor, the APJ receptor, in the intestine and the extent to which apelin exerts either a protective role, a healing role or both on the intestinal epithelium in animal models of experimental colitis.  Apelin is a recently discovered peptide that is the endogenous ligand for a G-protein-linked “orphan receptor” called the APJ receptor.  Apelin is expressed in the gastrointestinal (GI) tract and secreted into the gut lumen as well as the systemic circulation.

Our working hypotheses are that apelin is a potent mitogen for the intestinal epithelium and that apelin will exert a protective and/or healing action on the intestinal epithelium in patients with IBD.  Preliminary data demonstrate that apelin-13 is a potent mitogen for gut epithelial cells in vitro.

Our Specific Aims are:  Aim 1 - To test the hypothesis that intestinal expression of apelin and the APJ receptor are altered in patients with Inflammatory Bowel Disease (IBD).  Aim 2 - To test the hypothesis that apelin exerts a protective role on the intestinal epithelium in a rat model of experimental colitis.  Aim 3 - To test the hypothesis that apelin will promote epithelial healing in a rat model of experimental colitis.  Aim 4 - To test the hypothesis that apelin exerts its protective and/or healing activity by stimulation of trophic gut peptides and activation of MAPK.  In our studies, we intend to demonstrate that apelin is a strong mitogen and repair agent for the intestinal epithelium in animal models of IBD and that apelin has potential for stimulation of intestinal epithelial growth and repair in patients with IBD.  We will also define apelin and APJ expression profiles in intestinal tissue specimens from harvested rats having experimental colitis and from IBD patients.  These studies may lead to development of novel apelin analogues and therapeutic strategies that will benefit IBD and Crohn's disease patients.