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Non‐proteolytic house dust mite allergen, Der p 2, upregulated expression of tight junction molecule claudin‐2 associated with Akt/GSK‐3β/β‐catenin signaling pathway
Author(s) -
Wang WeiChun,
Tsai JawJi,
Kuo ChengYi,
Chen HanMin,
Kao ShaoHsuan
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23067
Subject(s) - claudin , occludin , tight junction , microbiology and biotechnology , protein kinase b , phosphorylation , chemistry , signal transduction , a549 cell , kinase , pi3k/akt/mtor pathway , phosphatidylinositol , biology , cell , biochemistry
Non‐proteolytic group 2 allergen, Der p 2 (DP2) is known as a major allergen derived from house dust mite Dermatophagoides pteronyssinus . Paracellular epithelial barrier, being composed of a number of tight junction (TJ) molecules, plays pivotal roles in resistance of pathogen invading. However, whether DP2 affects epithelial TJ molecules is unclear. Therefore, we aimed to investigate the effects of DP2 on epithelial TJ molecules, and the mechanism by which expression of junction molecules is regulated by DP2. Cell cycle and mRNA expression of TJ proteins of lung alveolar cell A549 were analyzed by RT‐PCR and flow cytometry. Level of claudin‐2, subcellular distribution of β‐catenin and kinase activation was determined using immunoblot. Our findings revealed that DP2 had no significant influence on cell cycle distribution but affected mRNA expression of TJ molecules including claudin‐2, occludin, and ZO‐1 in A549 cells. Our results showed that DP2 significantly elevated level of claudin‐2 and increased expression and nuclear translocation of β‐catenin. Moreover, DP2 enhanced the phosphorylation of glycogen synthase kinase‐3β (GSK‐3β) and its potential upstream regulator Akt. The DP2‐induced claudin‐2 expression was also suppressed by GSK‐3β inhibitor (lithium chloride) and phosphatidyl inositol 3‐phosphate kinase (PI3K) inhibitor (wortamannin). Taken together, these findings showed that DP2 increased claudin‐2 expression and its cell surface distribution in A549 cells, which may attribute to phosphorylation of GSK‐3β and Akt and the consequent increase and nuclear translocation of β‐catenin. It is suggested that presence of DP2 may alter epithelial junction by regulating expression of TJ molecules. J. Cell. Biochem. 112: 1544–1551, 2011. © 2011 Wiley‐Liss, Inc.