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Publication : Contribution of tight junction proteins to ion, macromolecule, and water barrier in keratinocytes.

First Author  Kirschner N Year  2013
Journal  J Invest Dermatol Volume  133
Issue  5 Pages  1161-9
PubMed ID  23407391 Mgi Jnum  J:198003
Mgi Id  MGI:5495079 Doi  10.1038/jid.2012.507
Citation  Kirschner N, et al. (2013) Contribution of tight junction proteins to ion, macromolecule, and water barrier in keratinocytes. J Invest Dermatol 133(5):1161-9
abstractText  Tight junctions (TJs) form a selective barrier for ions, water, and macromolecules in simple epithelia. In keratinocytes and epidermis, TJs were shown to be involved in individual barrier functions. The absence of the TJ protein claudin-1 (Cldn1) in mice results in a skin-barrier defect characterized by lethal water loss. However, detailed molecular analyses of the various TJ barriers in keratinocytes and the contribution of distinct TJ proteins are missing. Herein, we discriminate TJ-dependent paracellular resistance from transcellular resistance in cultured keratinocytes using the two-path impedance spectroscopy. We demonstrate that keratinocyte TJs form a barrier for Na(+), Cl(-), and Ca(2+), and contribute to barrier function for water and larger molecules of different size. In addition, knockdown of Cldn1, Cldn4, occludin, and zonula occludens-1 increased paracellular permeabilities for ions and larger molecules, demonstrating that all of these TJ proteins contribute to barrier formation. Remarkably, Cldn1 and Cldn4 are not critical for TJ barrier function for water in submerged keratinocyte cultures. However, Cldn1 influences stratum corneum (SC) proteins important for SC water barrier function, and is crucial for TJ barrier formation for allergen-sized macromolecules.
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