Ectopic Epithelial Deaminase in IBD
Final rept. 28 Sep 2012-27 Feb 2014
MASSACHUSETTS GENERAL HOSPITAL BOSTON
Pagination or Media Count:
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.
- Medicine and Medical Research