Aberrant expression of the polarity complex atypical PKC and non-muscle myosin IIA in active and inactive inflammatory bowel disease |
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Authors: | Wald Flavia A Forteza Radia Diwadkar-Watkins Runa Mashukova Anastasia Duncan Robert Abreu Maria T Salas Pedro J |
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Institution: | (1) Department Cell Biology and Anatomy, University of Miami, Miller School of Medicine, R-124, P.O. Box 016960, Miami, FL 33101, USA;(2) Department of Pediatrics, University of Miami, Miller School of Medicine, Miami, FL, USA;(3) Department of Epidemiology and Public Health, University of Miami, Miller School of Medicine, Miami, FL, USA;(4) Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA; |
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Abstract: | Epithelial barrier function is contingent on appropriate polarization of key protein components. Work in intestinal epithelial
cell cultures and animal models of bowel inflammation suggested that atypical PKC (aPKC), the kinase component of the Par3–Par6
polarity complex, is downregulated by pro-inflammatory signaling. Data from other laboratories showed the participation of
myosin light chain kinase in intestinal inflammation, but there is paucity of evidence for assembly of its major target, non-muscle
myosin II, in inflammatory bowel disease (IBD). In addition, we showed before that non-muscle myosin IIA (nmMyoIIA) is upregulated
in intestinal inflammation in mice and TNFα-treated Caco-2 cells. Thus far, it is unknown if a similar phenomena occur in
patients with IBD. Moreover, it is unclear whether aPKC downregulation is directly correlated with local mucosal inflammation
or occurs in uninvolved areas. Frozen sections from colonoscopy material were stained for immunofluorescence with extensively
validated specific antibodies against phosphorylated aPKC turn motif (active form) and nmMyoIIA. Inflammation was scored for
the local area from where the material was obtained. We found a significant negative correlation between the expression of
active aPKC and local inflammation, and a significant increase in the apical expression of nmMyoIIA in surface colon epithelia
in inflamed areas, but not in non-inflamed mucosa even in the same patients. Changes in aPKC and nmMyoIIA expression are likely
to participate in the pathogenesis of epithelial barrier function in response to local pro-inflammatory signals. These results
provide a rationale for pursuing mechanistic studies on the regulation of these proteins. |
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