Aberrant expression of the polarity complex atypical PKC and non-muscle myosin IIA in active and inactive inflammatory bowel disease

Flavia A. Wald, Radia Forteza, Runa Diwadkar-Watkins, Anastasia Mashukova, Robert Duncan, Maria T Abreu, Pedro J Salas

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)331-338
Number of pages8
JournalVirchows Archiv
Volume459
Issue number3
DOIs
StatePublished - Sep 1 2011

Fingerprint

Nonmuscle Myosin Type IIA
Inflammatory Bowel Diseases
Inflammation
Down-Regulation
Myosin Type II
Myosin-Light-Chain Kinase
Caco-2 Cells
Frozen Sections
Colonoscopy
Fluorescent Antibody Technique
Colon
Mucous Membrane
Proteins
Phosphotransferases
Epithelium
Animal Models
Cell Culture Techniques
Epithelial Cells
Antibodies

Keywords

  • Crohn's disease
  • Epithelial polarity
  • Non-muscle myosin IIA
  • PKCζ
  • PKCι
  • Ulcerative colitis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Molecular Biology

Cite this

Aberrant expression of the polarity complex atypical PKC and non-muscle myosin IIA in active and inactive inflammatory bowel disease. / Wald, Flavia A.; Forteza, Radia; Diwadkar-Watkins, Runa; Mashukova, Anastasia; Duncan, Robert; Abreu, Maria T; Salas, Pedro J.

In: Virchows Archiv, Vol. 459, No. 3, 01.09.2011, p. 331-338.

Research output: Contribution to journalArticle

Wald, Flavia A. ; Forteza, Radia ; Diwadkar-Watkins, Runa ; Mashukova, Anastasia ; Duncan, Robert ; Abreu, Maria T ; Salas, Pedro J. / Aberrant expression of the polarity complex atypical PKC and non-muscle myosin IIA in active and inactive inflammatory bowel disease. In: Virchows Archiv. 2011 ; Vol. 459, No. 3. pp. 331-338.
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