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Claudin‐4 is required for EGFR‐mediated alveolar epithelial migration
Author(s) -
Rokkam Deepti,
Ho Gwendolyn,
Frank James A.
Publication year - 2010
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.24.1_supplement.999.3
Subject(s) - claudin , tight junction , wound healing , microbiology and biotechnology , epidermal growth factor receptor , paracellular transport , cancer research , chemistry , cell migration , receptor , biology , cell , immunology , permeability (electromagnetism) , biochemistry , membrane
Claudin‐4 is tetraspan membrane protein known to play a role in paracellular conductance at tight junctions. Recent studies have shown an uncharacteristic diffuse localization of this protein in epithelial injury and this change in protein trafficking remains unexplained. It is our hypothesis that claudin‐4 plays a role in response to injury. To test this hypothesis, we utilized an alveolar epithelial type 2 cell scratch‐wound healing model. Claudin‐4 expression increased significantly with wounding whereas other claudins remained unchanged. Claudin‐4 expression was higher only in cells along the wound edge, and the protein was widely distributed in the cells. This change in trafficking was unique to claudin‐4 compared with other claudins and zona occludens‐1 (ZO‐1). Inhibition of claudin‐4 with a blocking peptide or siRNA delayed wound healing, indicating a potential role in repair. Since previous studies have shown claudin‐4 is induced by epidermal growth factor (EGF), we studied the activation of its receptor (EGFR) in this model. EGFR was activated along the wound edge in a pattern similar to the increase in claudin‐4. Inhibition of EGFR by AG1478 blocked the increase in claudin‐4 and delayed wound healing comparably to inhibition of claudin‐4 alone. We propose that expression of claudin‐4 is locally induced in wounded epithelia by EGFR and that claudin‐4 plays a novel role in EGFR‐mediated wound healing.