3rd Annual BMRP Investigator Meeting - Abstract

Increased Colonic Apelin Expression during Experimental Colitis in Rodents and in Humans with IBD

George H. Greeley, Jr.^a, Suimin Qiu, Guiyun Wang, Carol DeLa Motte, Hui-Qun Wang and Ella W. Englander

Department of Surgery, University of Texas at Galveston (Galveston, Texas, U.S.A.)

Apelin is a recently discovered peptide that is expressed in the gastrointestinal (GI) tract along with its receptor, the APJ receptor.  Apelin can stimulate GI epithelial proliferation.  The aim of this study was to determine the extent to which colonic apelin expression is activated in rodents during experimental colitis and in humans with inflammatory bowel disease (IBD).  

Methods: Colonic apelin production was examined at different intervals after induction of experimental colitis by oral administration of sodium dextran sulfate (DSS) for 7d in mice and 5d in rats.  Colonic apelin mRNA levels were monitored by real-time RT-PCR and apelin peptide by immunohistochemistry (IHC).  Colonic mucosa of ulcerative colitis (UC) and Crohn’s disease (CD) patients was immunostained for apelin.  

Results: Induction of experimental colitis in rodents increased colonic apelin mRNA levels significantly.  Apelin expression increased 2-3-fold during induction of acute colitis and gradually decreased after DSS was discontinued.  In mice (control: 0.22±.06) and in rats (control: 0.27±.06) one, two and three weeks after start of DSS, colonic apelin mRNA levels were 0.49±.08*, 0.5±.06* and 0.32±.03; and 0.85±.15*, 0.5±.05* and 0.2±.01, respectively (*=P<0.05 vs. control).  In rodents, immunostaining showed a greatly increased apelin peptide production in the stem cell region at the gland base, in epithelial cells along the length of the tubular gland and in the surface epithelium.  In both UC and CD patients, IHC revealed increased production of apelin peptide in the colonic stem cell region and surface epithelium when compared to normal colonic mucosa. Apelin shows a cytoplasmic localization.

Conclusions and Discussion: Findings indicate that colonic apelin expression and peptide production increase significantly during experimental colitis in rodents.  In humans with IBD, colonic apelin peptide production is also increased dramatically.  Because apelin exerts a proliferative action on the intestinal epithelium, the increased apelin expression during experimental colitis in rodents and during IBD in humans may reflect an adaptive response to stimulate epithelial proliferation and mucosal healing.

^aPrincipal Investigator