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Leaky protein claudin2 is directly upregulated in Salmonella infected intestinal epithelial cells
Author(s) -
Sun Jun,
Zhang Yongguo,
Wu Shaoping,
Xia Yinglin
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.650.13
Subject(s) - salmonella , immunostaining , gene knockdown , intestinal epithelium , tight junction , biology , downregulation and upregulation , microbiology and biotechnology , epithelium , claudin , intestinal mucosa , cytoplasm , cell culture , immunology , bacteria , gene , immunohistochemistry , medicine , biochemistry , genetics
To regulate cellular function, claudins interact structurally and functionally with membrane and scaffolding proteins via their cytoplasmic domain. In particular, claudin2 is known to be a leaky protein that contributes to inflammatory bowel disease and colon cancer. However, the involvement of claudin2 in bacterial infection remains unknown. We hypothesized that Salmonella disrupts tight junctions for its own benefit by elevating the claudin2 in the intestine. Using a Salmonella‐colitis mouse model and cultured intestinal epithelial cells, we found that pathogenic Salmonella colonization significantly increases the levels of claudin2 protein and mRNA, but not that of claudin3 or 7 in the colon, in a time‐dependent manner. Immunostaining studies showed that the distribution of claudin2 moved from the bottoms of the crypts to the middle of intestinal epithelium. In vitro, Salmonella stimulated claudin2 expression in the human intestinal epithelial cells. Further analysis by siRNA knockdown revealed that claudin2 is necessary for the Salmonella‐mediated cell permeability. Inhibitor assays demonstrated that this regulation is mediated through the EGFR pathway and the downstream protein JNK. Our study suggests the possibility of blocking claudin2 as a potential therapeutic strategy to prevent bacterial invasion.