4.6 Article

Altered expression of S100 fused-type proteins in an atopic dermatitis skin model

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EXPERIMENTAL DERMATOLOGY
卷 -, 期 -, 页码 -

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WILEY
DOI: 10.1111/exd.14797

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atopic dermatitis; filaggrin; S100 fused-type proteins; three-dimensional skin equivalent; type 2 cytokines

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This study investigated the effects of IL-4 and IL-13 and the downregulation of FLG on the expression of S100 fused-type proteins in a three-dimensional AD skin model. The results showed that the expression of FLG, FLG2, HRNR, and TCHH was decreased, while that of RPTN was increased in the AD skin model. Additionally, FLG knockdown resulted in increased expression of HRNR. These findings suggest that the expression of fused-S100 type protein family members may vary in AD and play different roles in its pathogenesis.
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with elevated interleukin (IL)-4 and IL-13 signatures and extensive barrier dysfunction, which is correlated with the downregulation of filaggrin (FLG). FLG is a member of the S100 fused-type protein family and this family also includes cornulin (CRNN), filaggrin-2 (FLG2), hornerin (HRNR) repetin (RPTN), trichohyalin (TCHH) and trichohyalin-like 1 (TCHHL1). The present study aimed to examine the effects of IL-4 and IL-13 and the downregulation of FLG on the expression of S100 fused-type proteins using a three-dimensional (3D) AD skin model by immunohistochemical study and quantitative polymerase chain reaction. In the 3D AD skin model, which was generated by a stimulation of recombinant IL-4 and IL-13, the expression of FLG, FLG2, HRNR and TCHH was decreased, while that of RPTN was increased in comparison to the 3D control skin. In the FLG knockdown (KD) 3D skin model, which was generated using FLG siRNA, the expression of HRNR was increased. The expression of the other proteins did not differ to a statistically significant extent. The expression of fused-S100 type protein family members may differ in AD skin. This suggests that these proteins play different roles in the pathogenesis of AD.

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