Abstract
Chronic inflammatory diseases of the intestines such as inflammatory bowel disease (IBD) are characterized by disturbed epithelial contacts and increased intestinal permeability. The actin cytoskeleton and its regulators are critical for these features. Analyzing cortactin‐KO mice, we found that the actin‐binding molecule cortactin (CTTN) controls vascular permeability. However, it is unknown if CTTN also regulates intestinal epithelial permeability. Thus, we generated a stable CTTN‐depleted Caco‐2 cell line that showed reduced transepithelial resistence (TER) and increased paracellular flux of 4 kDa FITC‐dextran. In these cells, we also observed a less developed cortical actin ring and internalization of occludin and ZO‐1. However, CTTN depletion did not cause increased apoptosis. CTTN‐KO mice also showed increased basal permeability in the colon. In healthy human colon tissue biopsies, we found that CTTN colocalized with actin and the tight junction protein ZO‐1. By contrast, in IBD patients, we observed strong internalization of CTTN resulting in a loss of colocalization with actin and ZO‐1. Our data imply that CTTN regulates intestinal permeability by controlling actin dynamics at cell contacts to stabilize epithelial junctions.Grant Funding Source: CONACYT 179895
Published Version
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