Accession Number : ADA618502


Title :   CLMP-Mediated Regulation of Intestinal Homeostasis in IBD


Descriptive Note : Annual rept. 30 Sep 2013-29 Sep 2014


Corporate Author : EMORY UNIV ATLANTA GA


Personal Author(s) : Nusrat, Asma ; Parkos, Charles A ; Luissint, Anny-Claude ; Bennett, Ashley


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a618502.pdf


Report Date : Oct 2014


Pagination or Media Count : 16


Abstract : The intestinal mucosa is composed by a single layer of epithelial cells that forms a selective physical barrier allowing the passage of nutrients and solutes while protecting the body against external antigens. The impairment of the intestinal barrier function is well-appreciated to negatively contribute to the pathogenesis of inflammatory bowel disease. Barrier properties are due to intercellular junction proteins and among these proteins are found the members of the Cortical Thymocyte marker in Xenopus (CTX) family. CAR-Like Membrane Protein (CLMP) belongs to the CTX family, however, its function in the intestine has been poorly investigated. The global aim of our project is to characterize the role of CLMP in the intestinal mucosal homeostasis and inflammatory diseases. During this first year of the research period, we studied the role of CLMP in intestinal epithelial cell proliferation, migration and barrier function under normal conditions. Our results show that CLMP is concentrated at contacts between adjacent epithelial cells in adult mouse colon and human intestinal epithelial cell lines (IECs). CLMP overexpression in IECs decreases cell proliferation and prevents the growth of subcutaneous xenograft tumors in Rag1 -/- mice. Interestingly, CLMP overexpression in IECs enhances cell-cell interactions and promotes epithelial wound healing after injury. In contrast, CLMP down-regulation increases cell proliferation and diminishes epithelial barrier function. In conclusion, our findings strongly suggest that CLMP plays a key role in regulation of several aspects of the mucosal epithelial homeostasis including barrier properties, cell proliferation and wound repair.


Descriptors :   *HOMEOSTASIS , *INTESTINES , ANTIGENS , BARRIERS , CELLS(BIOLOGY) , DISEASES , EPITHELIUM , FUNCTIONS , HEALING , INFLAMMATION , INTERACTIONS , MUCOUS MEMBRANES , NEOPLASMS , NUTRIENTS , PATHOGENESIS , PROTEINS , SOLUTES , SURGICAL TRANSPLANTATION , WOUNDS AND INJURIES


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE