Ectopic Epithelial Deaminase in IBD
Abstract
This project is designed to dissect out the primary event that initiates the alteration of epithelial cell homeostasis in inflammatory bowel disease (IBD). Our hypothesis is that activation-induced cytidine deaminase (AID, a DNA-modifying enzyme), which is ectopically expressed in epithelial cells only under intestinal inflammatory condition, is primarily responsible for the initiation of epithelial homeostatic alteration through epigenetic modification. Throughout this project, we have successfully developed fate-mapping double reporter mouse system that allows us to closely examine epithelial cells with prior AID expression versus those without it. By utilizing this mouse system, we have found that AID is expressed by some epithelial crypts under acute intestinal inflammatory condition induced by administration of dextran sulfate sodium (DSS), whereas it is expressed by majority of epithelial crypts during a chronic phase of inflammation. We have also found a possible involvement of AID in the epigenetic modification of some specific genes such as signaling transducers and activators of transcription 3 (STAT3). We initially hypothesized the deleterious role of AID in colitis, but our new data rather suggest the protective role. These findings not only suggest an unexpected function of AID but also have a potential to provide a rationale for the development of novel therapeutic strategy for saving the lives of patients with IBD.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2014
- Accession Number
- ADA610011
Entities
People
- Atsushi Mizoguchi
Organizations
- Massachusetts General Hospital