Contribution of tight junction proteins to ion, macromolecule, and water barrier in keratinocytes
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Contribution of tight junction proteins to ion, macromolecule, and water barrier in keratinocytes. / Kirschner, Nina; Rosenthal, Rita; Furuse, Mikio; Moll, Ingrid; Fromm, Michael; Brandner, Johanna M.
in: J INVEST DERMATOL, Jahrgang 133, Nr. 5, 01.05.2013, S. 1161-9.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Contribution of tight junction proteins to ion, macromolecule, and water barrier in keratinocytes
AU - Kirschner, Nina
AU - Rosenthal, Rita
AU - Furuse, Mikio
AU - Moll, Ingrid
AU - Fromm, Michael
AU - Brandner, Johanna M
PY - 2013/5/1
Y1 - 2013/5/1
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Membrane Permeability
KW - Cells, Cultured
KW - Claudin-1
KW - Claudin-4
KW - Ions
KW - Keratinocytes
KW - Macromolecular Substances
KW - Male
KW - Mice
KW - Mice, Knockout
KW - Models, Animal
KW - Occludin
KW - Tight Junction Proteins
KW - Tight Junctions
KW - Water
KW - Zonula Occludens-1 Protein
U2 - 10.1038/jid.2012.507
DO - 10.1038/jid.2012.507
M3 - SCORING: Journal article
C2 - 23407391
VL - 133
SP - 1161
EP - 1169
JO - J INVEST DERMATOL
JF - J INVEST DERMATOL
SN - 0022-202X
IS - 5
ER -