7th Annual BMRP Investigator Meeting - Abstract

The Differential Expression of microRNAs in Inflammatory Bowel Disease and Murine Colitis
 
Feng Wu1, Simin Zhang1, Theodore M. Bayless1, Steven R. Brant1,2 and John H. Kwon1,a
 
1The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Division of Gastroenterology, Johns Hopkins University Medical Institutions and 2Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, (Baltimore, Maryland, U.S.A.)
 
MicroRNAs, a group of small, non-coding RNAs encoded in the human genome, are increasingly recognized as major negative regulators of gene expression in many processes, including development, cancer and inflammation.  We previously demonstrated that eleven microRNAs are differentially expressed in sigmoid colon pinch biopsy tissues from patients with active ulcerative colitis and that microRNAs regulate intestinal chemokine expression. The aim of this study is to further characterize microRNA expression in IBD tissues and to explore the role of microRNAs in murine models of colitis. Using microRNA microarrays and validation RTPCR, a further analysis of sigmoid colon pinch biopsy samples reveals 13 differentially expressed microRNAs in active Crohn’s disease. These microRNAs are distinct from four microRNAs differentially expressed in Crohn’s ileitis tissues. In addition, a preliminary expression profile of blood-based microRNAs in IBD patients demonstrate significant differences in microRNAs expressed in blood as compared to colonoscopic pinch biopsy samples. We further identify 4 up-regulated and 23 down-regulated microRNAs in the TNBS model of murine colitis. We successfully demonstrate the delivery of microRNA inhibitors and mimics to the colonic epithelial cells of mice. Further studies will determine whether microRNA expression profiles in blood and intestinal tissues can be used in the development of a diagnostic test for IBD. In addition, we will examine whether the alteration of intestinal microRNA expression influences the pathogenesis of colitis.
  
aPrincipal Investigator