Lay Summary

Proposal No. IBD-0020R
Principal Investigator:  Giovanni Monteleone, M.D., Ph.D.
Applicant Organization:  University Tor Vergata of Rome (Italy)
Project Title:  Role of Smad7, an inhibitor of TGF-beta1 signaling, in chronic intestinal inflammation
Period of Award:  September 1, 2002- November 30, 2004

Despite considerable advances in our understanding of inflammatory bowel disease (IBD) pathogenesis, it remains unclear why production of inflammation suppressor molecules is not sufficient to limit the intestinal inflammation.  We have recently shown that the activity of transforming growth factor-beta-1 (TGF-β1), a powerful mucosal inflammation suppressor, is defective in IBD and that this is associated with enhanced production of Smad7, an intracellular protein that binds to the TGF-β1 receptor and blocks TGF-β1 activity.  Suppression of Smad7 restores TGF-β1 signaling, reducing inflammatory cytokine (regulator of white cell activity) production and decreasing inflammation.

The project will investigate mechanisms by which TGF-β1 promotes and/or maintains intestinal homeostasis and characterize the involvement of Smad7 in the activation or suppression of important inflammatory pathways in IBD.  The proposed experiments will help us to understand if inhibition of Smad7 may be a novel and useful therapeutic approach for IBD.