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Claudin‐1 as a target for modulation of epidermal barriers (1062.6)
Author(s) -
Nakajima Misaki,
Yamashita Mayo,
Watari Akihiro,
Yagi Kiyohito,
Fukasawa Masayoshi,
Kondoh Masuo
Publication year - 2014
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.28.1_supplement.1062.6
Subject(s) - claudin , tight junction , microbiology and biotechnology , epithelium , chemistry , in vitro , barrier function , biology , biochemistry , genetics
Epithelium plays pivotal roles in barriers that separate the inside of the body from the outside environment. Passage across epithelial barriers is the first step in drug absorption. Epidermal absorption is an ideal route for drug administration because it is non‐invasive and easily controlled. Claudin‐1 (CLDN1) seals tight junctions in the stratum granulosum, but whether modulation of CLDN1 enhances epidermal permeability is unclear. We investigated the effect of an anti‐CLDN1 antibody on the epidermal epithelial barrier by using human epidermal keratinocytes (NHEK), a popular in vitro model of human epithelial cell sheets. Immunoblot and FACS analyses showed that CLDN1 was expressed on NHEK cell membranes. Treatment of NHEK monolayers with anti‐CLDN1 antibody decreased the integrity of tight junctions between adjacent cells and enhanced the permeation of solutes across the cell sheets. Furthermore, treatment of Caco‐2 cell monolayers, a popular model of the human intestinal barrier that expresses CLDN1 and CLDN4, with anti‐CLDN4, but not treatment with anti‐CLDN1, decreased the integrity of tight junctions. These findings suggest that CLND1 may be a target for specific modulation of epidermal barrier. Grant Funding Source : supported by the Ministry of Health, Labor, and Welfare of Japan