CLMP-Mediated Regulation of Intestinal Homeostasis in IBD
Annual rept. 30 Sep 2013-29 Sep 2014
EMORY UNIV ATLANTA GA
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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.
- Medicine and Medical Research