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/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

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@article{2c86f960fdfc4527b0438516c84e2fc2,
title = "Contribution of tight junction proteins to ion, macromolecule, and water barrier in keratinocytes",
abstract = "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.",
keywords = "Animals, Cell Membrane Permeability, Cells, Cultured, Claudin-1, Claudin-4, Ions, Keratinocytes, Macromolecular Substances, Male, Mice, Mice, Knockout, Models, Animal, Occludin, Tight Junction Proteins, Tight Junctions, Water, Zonula Occludens-1 Protein",
author = "Nina Kirschner and Rita Rosenthal and Mikio Furuse and Ingrid Moll and Michael Fromm and Brandner, {Johanna M}",
year = "2013",
month = may,
day = "1",
doi = "10.1038/jid.2012.507",
language = "English",
volume = "133",
pages = "1161--9",
journal = "J INVEST DERMATOL",
issn = "0022-202X",
publisher = "NATURE PUBLISHING GROUP",
number = "5",

}

RIS

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 -