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Claudin-1 decrease impacts epidermal barrier function in atopic dermatitis lesions dose-dependently

delete2020-02-06
delete88
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OA
AI
S
Sophia Bergmann
B
Barbara von Buenau
S
Sabine Vidal‐y‐Sy
M
Marek Haftek
E
Ewa Wladykowski
P
Pia Houdek
S
Susanne Lezius
H
Hélène Duplan
K
Katja Bäsler
S
Stephan Dähnhardt‐Pfeiffer
C
Christian Gorzelanny
S
Stefan W. Schneider
E
Elke Rodríguez
D
Dora Stölzl
S
Stephan Weidinger
J
Johanna M. Brandner *
DOI:10.1038/s41598-020-58718-9delete
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摘要

摘要

En 中文
The transmembrane protein claudin-1 is a major component of epidermal tight junctions (TJs), which create a dynamic paracellular barrier in the epidermis. Claudin-1 downregulation has been linked to atopic dermatitis (AD) pathogenesis but variable levels of claudin-1 have also been observed in healthy skin. To elucidate the impact of different levels of claudin-1 in healthy and diseased skin we determined claudin-1 levels in AD patients and controls and correlated them to TJ and skin barrier function. We observed a strikingly broad range of claudin-1 levels with stable TJ and overall skin barrier function in healthy and non-lesional skin. However, a significant decrease in TJ barrier function was detected in lesional AD skin where claudin-1 levels were further reduced. Investigations on reconstructed human epidermis expressing different levels of claudin-1 revealed that claudin-1 levels correlated with inside-out and outside-in barrier function, with a higher coherence for smaller molecular tracers. Claudin-1 decrease induced keratinocyte-autonomous IL-1 beta expression and fostered inflammatory epidermal responses to non-pathogenic Staphylococci. In conclusion, claudin-1 decrease beyond a threshold level results in TJ and epidermal barrier function impairment and induces inflammation in human epidermis. Increasing claudin-1 levels might improve barrier function and decrease inflammation and therefore be a target for AD treatment.
Keyword:
TIGHT JUNCTIONS
STAPHYLOCOCCUS-AUREUS
STRATUM GRANULOSUM
UNINVOLVED SKIN
FILAGGRIN
KERATINOCYTES
PENETRATION
RESISTANCE
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Scientific Reports 封面图
Scientific Reports
IF:
3.9
论文数:
28.0W
被引数:
83.5W

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U
Universite Claude Bernard Lyon 1
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2.4W
论文数: 1.7W
被引数: 156
U
university of hamburg
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3.7W
论文数: 2.9W
被引数: 30
C
cnrs - national institute for biology (insb)
学者数:
1.5W
论文数: 9.5K
被引数: 9
U
University Medical Center Hamburg-Eppendorf
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论文数: 1.3W
被引数: 2.0W
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