Enhancement of barrier function by overexpression of claudin-4 in tight junctions of submandibular gland cells |
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Authors: | Hiromi Michikawa Junko Fujita-Yoshigaki Hiroshi Sugiya |
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Institution: | (1) Department of Physiology, Nihon University School of Dentistry at Matsudo, Sakaecho-nishi 2-870-1, Matsudo Chiba, 271-8587, Japan;(2) Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Sakaecho-nishi 2-870-1, Matsudo Chiba, 271-8587, Japan;(3) Present address: Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Miyama 2-2-1, Funabashi Chiba, 274-8510, Japan |
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Abstract: | In salivary glands, primary saliva is produced by acini and is modified by the reabsorption and secretion of ions in the ducts.
Thus, the permeability of intercellular junctions in the ducts is considered to be lower than in the acini. We have examined
the relationship between the expressed claudin isotypes and the barrier functions of tight junctions in a submandibular gland
epithelial cell line, SMIE. SMIE cells were originally derived from rat submandibular duct cells, but their barrier functions
are not as efficient as those of Madin-Darby canine kidney cells. Large molecules, such as 70-kDa dextran, diffuse across
the monolayers, although E-cadherin and occludin, adherens junction and tight junction proteins, respectively, are expressed
in SMIE cells. Claudin-3 protein has also been detected, but the expression level of claudin-3 mRNA is much lower than in
the original submandibular glands. Other claudins including claudin-4 (originally expressed in the duct cells) have not been
detected. Because of the limited expression of claudins, SMIE cells are suitable for studying the role(s) of claudins. To
examine the function of claudin-4 in submandibular glands, we have overexpressed green fluorescence protein (GFP)-fused claudin-4
in SMIE cells. Cells that express GFP-fused claudin-4 have a higher transepithelial electrical resistance and a lower permeability
of 70-kDa dextran, although the expression levels of occludin and claudin-3 are hardly affected. Therefore, claudin-4 plays
a role in the regulation of the barrier function of tight junctions in submandibular glands.
This work was supported by Grants-in-Aid for scientific research from the Ministry of Education, Science, Culture, Sports,
and Technology of Japan (16591868), by a Nihon University Multidisciplinary Research Grant for 2006 and 2007, and by a Grant-in-Aid
for a 2003 Multidisciplinary Research Project from MEXT. |
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Keywords: | Salivary gland Submandibular gland Tight junction Claudin Paracellular transport SMIE cell line Rat (Sprague Dawley) |
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