Role of Claudin-2 in Inflammatory Diseases and Colon Cancer

Project: Research project

Description

DESCRIPTION (provided by applicant): Increased mucosal permeability is a key characteristic of the inflammatory bowel disease (IBD). The claudin family of proteins constitutes the tight junctions (TJs), which are the sole determinants of the paracellular permeability in an intact epithelium. Importantly, a common finding from the analysis of the IBD (Crohn's and Ulcerative Colitis) patient samples and related animal models is that claudin-2 expression is highly upregulated in the IBD. In the claudin family, Claudin-2 is unique as its expression correlates with the epithelial leakiness. However, it is also noteworthy that the colonic claudin-2 is expressed among the undifferentiated colonocytes at the crypt base, the proliferative zone. Furthermore, outcome from our preliminary studies and recently published studies from other labs suggest potential correlation of claudin-2 expression with the colonic epithelial cell proliferation and/or migration. It is further noteworthy that claudin-2 is a target of the Wnt/ -catenin signaling. However, role of claudin-2 in the pathogenesis of IBD is not known. To investigate, we generated Villin-claudin-2 transgenic (Cl-2Tg) mice that overexpress claudin-2 in the colon, a condition similar to the IBD. Our studies using these mice have provided novel outcomes: 1) Colonic epithelial permeability in Cl-2Tg mice is significantly increased compared to the WT littermates (p
StatusFinished
Effective start/end date8/3/115/31/16

Funding

  • National Institutes of Health: $23,647.00
  • National Institutes of Health: $327,338.00
  • National Institutes of Health: $327,425.00
  • National Institutes of Health: $339,300.00
  • National Institutes of Health: $315,653.00
  • National Institutes of Health: $390,000.00

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Claudin-2
Colonic Neoplasms
Inflammatory Bowel Diseases
Permeability
Transgenic Mice
Claudins
Catenins
Tight Junctions
Ulcerative Colitis
Cell Movement
Colon
Epithelium
Animal Models
Epithelial Cells

ASJC

  • Medicine(all)