Organic osmolytes preserve the function of the developing tight junction in ultraviolet B-irradiated rat epidermal keratinocytes

Cécile El-Chami, Iain S. Haslam, Martin C. Steward, Catherine A. O'Neill

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Epidermal barrier function is provided by the highly keratinised stratum corneum and also by tight junctions (TJs) in the granular layer of skin. The development of the TJ barrier significantly deteriorates in response to ultraviolet B radiation (UVB). Following exposure to UVB, keratinocytes accumulate organic osmolytes, which are known to preserve cell volume during water stress. Since TJs are intimately associated with control of water homeostasis in skin, we hypothesised that there may be a direct influence of osmolytes on TJ development. Exposure of rat epidermal keratinocytes (REKs) to a single dose of UVB reduced the function of developing TJs. This was concomitant with dislocalisation of claudin-1 and claudin-4 from the keratinocyte plasma membrane, phosphorylation of occludin and elevation of reactive oxygen species (ROS). In the presence of organic osmolytes, these effects were negated but were independent of the effects of these molecules on cell volume, elevation of ROS or the gene expression of TJ proteins. These data suggest that organic osmolytes affect TJs via post-translational mechanism(s) possibly involving protection of the native conformation of TJ proteins.

Original languageEnglish
Article number5167
Number of pages12
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 26 Mar 2018

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Tight Junctions
Keratinocytes
Tight Junction Proteins
Radiation
Cell Size
Reactive Oxygen Species
Claudin-4
Claudin-1
Occludin
Skin
Dehydration
Cornea
Homeostasis
Phosphorylation
Cell Membrane
Gene Expression
Water

Cite this

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title = "Organic osmolytes preserve the function of the developing tight junction in ultraviolet B-irradiated rat epidermal keratinocytes",
abstract = "Epidermal barrier function is provided by the highly keratinised stratum corneum and also by tight junctions (TJs) in the granular layer of skin. The development of the TJ barrier significantly deteriorates in response to ultraviolet B radiation (UVB). Following exposure to UVB, keratinocytes accumulate organic osmolytes, which are known to preserve cell volume during water stress. Since TJs are intimately associated with control of water homeostasis in skin, we hypothesised that there may be a direct influence of osmolytes on TJ development. Exposure of rat epidermal keratinocytes (REKs) to a single dose of UVB reduced the function of developing TJs. This was concomitant with dislocalisation of claudin-1 and claudin-4 from the keratinocyte plasma membrane, phosphorylation of occludin and elevation of reactive oxygen species (ROS). In the presence of organic osmolytes, these effects were negated but were independent of the effects of these molecules on cell volume, elevation of ROS or the gene expression of TJ proteins. These data suggest that organic osmolytes affect TJs via post-translational mechanism(s) possibly involving protection of the native conformation of TJ proteins.",
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Organic osmolytes preserve the function of the developing tight junction in ultraviolet B-irradiated rat epidermal keratinocytes. / El-Chami, Cécile; Haslam, Iain S.; Steward, Martin C.; O'Neill, Catherine A.

In: Scientific Reports, Vol. 8, No. 1, 5167, 26.03.2018.

Research output: Contribution to journalArticle

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