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Loss of Cortactin is Associated with Intestinal Epithelial Barrier Dysfunction and Development of Colitis
Author(s) -
CitalánMadrid Alí,
García Alexander,
Vargas Hilda,
Betanzos Abigail,
Nava Porfirio,
Rottner Klemens,
Menningen Rudolf,
Schnoor Michael
Publication year - 2015
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.29.1_supplement.282.1
Subject(s) - cortactin , microbiology and biotechnology , occludin , tight junction , biology , cell , cytoskeleton , biochemistry
A stable intestinal epithelium is the basis for healthy intestines. Its dysfunction causes increased intestinal permeability and bacterial translocation that may eventually cause an aberrant immune response leading to chronic inflammatory diseases of the intestines such as inflammatory bowel disease (IBD). The actin cytoskeleton regulates epithelial barrier integrity but the role of actin regulators such as cortactin (CTTN) is not well understood. Analyzing CTTN‐KO mice, we found increased basal intestinal permeability similar to what has been shown in the vasculature. Using a CTTN‐depleted Caco‐2 cell line, we confirmed epithelial dysfunction by reduced transepithelial resistance (TER), a weaker cortical actin ring, internalization of occludin and ZO‐1 and accelerated transmigration of neutrophils. Calcium‐switch assays revealed a strong delay in barrier formation without CTTN. While CTTN depletion did not cause increased apoptosis, we observed increased proliferation. Importantly, CTTN localized at cell contacts in colon biopsies of healthy individuals, whereas in IBD patients we observed strong translocation of CTTN into the cytosol and loss of colocalization with actin and ZO‐1. Our data imply that CTTN controls intestinal barrier integrity under basal conditions and that loss of CTTN triggers epithelial dysfunction as seen in IBD.

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