Lay Summary

Proposal No. IBD-0212
Principal Investigator:  John H. Kwon, M.D., Ph.D.
Applicant Organization:  Johns Hopkins University (Baltimore, Maryland, U.S.A.)
Project Title:  The differential expression of microRNA in ulcerative colitis patients and their regulation of MIP-2α expression
Period of Award:  July 1, 2007 –  January 31, 2010

Several studies have demonstrated that both ulcerative colitis (UC) and Crohn’s disease (CD) are associated with the sustained, increased expression of genes controlling inflammation and scar tissue formation. The ways these genes are controlled in IBD are not fully understood. However, the increased gene expression can result from an increased rate of messenger RNA (mRNA) production, a decreased mRNA degradation or an increased rate of protein production. MicroRNAs, which are a diverse group of very small RNAs, control gene expression by targeting mRNAs for breakdown or blocking the production of proteins. MicroRNAs are expressed differently in numerous cancers and some other human diseases. They have been implicated in the development of organs or tissues as well as in influencing cell growth and cell death. Recently, microRNAs were also shown to influence inflammation. However, their expression and function in chronic inflammatory diseases like IBD have not been examined.

We hypothesize that the sustained increased expression of genes involved in inflammation and scar tissue formation in IBD might be caused by a reduction in the amount of microRNAs that normally would turn off the expression of these genes. Our early results show that there are different amounts of certain microRNAs in tissues of patients with UC compared to normal, healthy people. These early results also show that microRNAs can control the colon tissue expression of macrophage inflammatory peptide (MIP)-2α, a molecule that attracts specific inflammatory cells (neutrophils) to areas of inflammation. In this proposal, we will confirm the expression of microRNAs in active UC patients compared to inactive UC and normal healthy people. We will also deepen our understanding of how microRNAs control the levels of MIP-2α and other inflammatory and scarring genes. We expect the results to increase our understanding of how inflammation is regulated in the intestine. Ultimately, these studies may lead to the development of microRNA-based treatments for IBD.