Proteolytic Regulation of the Intestinal Epithelial Barrier: Mechanisms and Interventions
Annual rept. 1 Sep 2012-31 Aug 2013
MARYLAND UNIV BALTIMORE SCHOOL OF MEDICINE
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Inflammatory bowel diseases are characterized by chronic, progressive and destructive inflammation of the gastrointestinal tract. The two main forms of inflammatory bowel diseases, Crohn s disease and Ulcerative Colitis, currently affect over 1 million Americans including military personnel, and the incidence among aging veterans is rising. Compromised intestinal barrier function underlies much of the pathology associated with many inflammatory bowel diseases. Matriptase is a membrane-anchored serine protease encoded by the Suppression of Tumorigenicity-14 ST14 gene that is required for epithelial barrier homeostasis. Here, we are investigating matriptase dysregulation and its contribution to the pathogenesis of acute colitis using the St14 hypomorphic mouse model of matriptase deficiency. The project uses a mouse model that is genetically deficient in matriptase and an experimental model of inflammatory colitis, to determine molecular processes by which matriptase protects barrier function in inflamed mucosa, and to define the mechanisms by which matriptase becomes decreased during inflammation associated with inflammatory bowel diseases. In the first year of this grant, our findings support a critical protective role for matriptase in restoring barrier function to injured intestinal mucosa, such that its down-regulation by IL-13 likely enhances excessive activation of the immune system.
- Medicine and Medical Research