The gastrointestinal epithelium plays a central role in maintaining and coordinating mucosal homeostasis and immunity. Intestinal epithelial barrier compromise in mucosal wounds is seen in many pathologic states that encompass inflammatory bowel diseases, ischemia, mechanical injury and surgical procedures. Coordinated epithelial cell migration and proliferation required for wound closure is a complex process that is not well understood. Our overarching hypothesis is that epithelial and immune cell mediators in the intestinal mucosa coordinate epithelial repair responses. Thus, the proposed studies will identify and characterize mechanisms by which lipid and protein mediators in the intestinal mucosa promote wound repair. Knowledge gained from these studies in the short term will provide a better understanding of basic mechanisms by which inflammatory cell and epithelial mediators control intestinal epithelial homeostasis and mucosal wound repair. In the long term these studies will aid in the development of new therapeutic strategies aimed at promoting intestinal mucosal wound repair.

Public Health Relevance

The lining of the gastrointestinal tract plays an important role in immune defense, which can be significantly compromised by conditions such as inflammatory bowel diseases, ischemia, mechanical injury and surgical procedures. This grant will address mechanisms by which the mucosal lining heals after such damage. Knowledge gained from these studies in the short term will provide a better understanding of basic mechanisms by which wound healing is controlled, and in the long term, these studies will aid in the development of new therapeutic strategies aimed at promoting mucosal wound repair.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01DK055679-16
Application #
8696334
Study Section
Gastrointestinal Mucosal Pathobiology Study Section (GMPB)
Program Officer
Carrington, Jill L
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Emory University
Department
Pathology
Type
Schools of Medicine
DUNS #
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Mitchell, Leslie A; Ward, Christina; Kwon, Mike et al. (2015) Junctional adhesion molecule A promotes epithelial tight junction assembly to augment lung barrier function. Am J Pathol 185:372-86
Jiang, Kun; Rankin, Carl R; Nava, Porfirio et al. (2014) Galectin-3 regulates desmoglein-2 and intestinal epithelial intercellular adhesion. J Biol Chem 289:10510-7
Weber, D A; Sumagin, R; McCall, I C et al. (2014) Neutrophil-derived JAML inhibits repair of intestinal epithelial injury during acute inflammation. Mucosal Immunol 7:1221-32
Alam, A; Leoni, G; Wentworth, C C et al. (2014) Redox signaling regulates commensal-mediated mucosal homeostasis and restitution and requires formyl peptide receptor 1. Mucosal Immunol 7:645-55
Neumann, Philipp-Alexander; Koch, Stefan; Hilgarth, Roland S et al. (2014) Gut commensal bacteria and regional Wnt gene expression in the proximal versus distal colon. Am J Pathol 184:592-9
Leoni, Giovanna; Alam, Ashfaqul; Neumann, Philipp-Alexander et al. (2013) Annexin A1, formyl peptide receptor, and NOX1 orchestrate epithelial repair. J Clin Invest 123:443-54
Rankin, Carl R; Hilgarth, Roland S; Leoni, Giovanna et al. (2013) Annexin A2 regulates *1 integrin internalization and intestinal epithelial cell migration. J Biol Chem 288:15229-39
Brazil, Jennifer C; Liu, Renpeng; Sumagin, Ronen et al. (2013) *3/4 Fucosyltransferase 3-dependent synthesis of Sialyl Lewis A on CD44 variant containing exon 6 mediates polymorphonuclear leukocyte detachment from intestinal epithelium during transepithelial migration. J Immunol 191:4804-17
Koch, S; Capaldo, C T; Hilgarth, R S et al. (2013) Protein kinase CK2 is a critical regulator of epithelial homeostasis in chronic intestinal inflammation. Mucosal Immunol 6:136-45
McConnell, Beth B; Kim, Samuel S; Yu, Ke et al. (2011) Kruppel-like factor 5 is important for maintenance of crypt architecture and barrier function in mouse intestine. Gastroenterology 141:1302-13, 1313.e1-6

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