Protective role of Galectin‐7 for skin barrier impairment in atopic dermatitis
Protective role of Galectin‐7 for skin barrier impairment in atopic dermatitis
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Galectin-7 对特应性皮炎皮肤屏障损伤的保护作用
DOI：
10.1111/cea.13672
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发表时间：
2020
影响因子：
6.1
通讯作者：
Tokura Yoshiki
中科院分区：
文献类型：
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作者：
Umayahara Takatsune;Shimauchi Takatoshi;Iwasaki Manami;Sakabe Jun‐ichi;Aoshima Masahiro;Nakazawa Shinsuke;Yatagai Tsuyoshi;Yamaguchi Hayato;Phadungsaksawasdi Pawit;Kurihara Kazuo;Tokura Yoshiki
背景特应性皮炎（AD）患者存在与Th 2优势型皮肤炎症相关的屏障障碍。半乳糖凝集素-7（Galectin-7，Gal-7）是一种可溶性非糖基化凝集素，在AD患者的皮层中高度表达。然而，AD皮损中Gal-7表达增加的生物学意义尚不清楚。我们旨在研究Gal-7在AD患者和IL-4/IL-13刺激的表皮角质形成细胞中的产生机制和功能作用。Gal-7水平也在单层正常人表皮角质形成细胞（NHEK）和三维（3D）重建的表皮中进行了测量，在存在或不存在IL-4/IL-13的情况下，有或没有Stat 3，Stat 6或Gal-7基因沉默。在AD患者中，血清Gal-7水平与经表皮水分丢失呈正相关。这些临床发现得到了我们的体外数据的证实，这些数据表明IL-4/IL-13促进了单层NHEK和3D重建表皮中内源性Gal-7的细胞外释放。这种机制是由IL-4/IL-13诱导的细胞损伤引起的，并通过敲低NHEK中的Stat 6而不是Stat 3来抑制。此外，我们在3D重建的表皮上进行了Gal-7敲低实验，结果表明内源性Gal-7可作为IL-4/IL-13诱导的细胞与细胞粘附和/或细胞与细胞外基质粘附破坏的保护剂。结论和临床意义我们的研究揭示了Gal-7的特性及其可能作为反映IL-4/IL-13诱导的AD皮肤屏障损伤的警报素的作用。
BackgroundAtopic dermatitis (AD) patients have a barrier disorder in association with Th2 dominant skin inflammation. Galectin‐7 (Gal‐7), a soluble unglycosylated lectin, is highly expressed in thestratum corneumof AD patients. However, the biological significance of increased Gal‐7 expression in AD skin lesions remains unclear.ObjectiveWe aimed to investigate the production mechanism and functional role of Gal‐7 in AD patients and IL‐4/IL‐13–stimulated epidermal keratinocytes.MethodsWe assessed the Gal‐7 expression levels in skin lesions and sera from AD patients. Gal‐7 levels were also measured in monolayered normal human epidermal keratinocytes (NHEKs) and 3‐dimensional (3D)–reconstructed epidermis in the presence or absence of IL‐4/IL‐13 with or without Stat3, Stat6 or Gal‐7 gene silencing.ResultsGal‐7 was highly expressed in thestratum corneumor intercellular space of AD lesional epidermis as assessed by thestratum corneumproteome analysis and immunohistochemistry. A positive correlation was noted between serum Gal‐7 level and transepidermal water loss in patients with AD. These clinical findings were corroborated by our in vitro data, which showed that IL‐4/IL‐13 facilitated the extracellular release of endogenous Gal‐7 in both monolayered NHEKs and 3D‐reconstructed epidermis. This machinery was caused by IL‐4/IL‐13–induced cell damage and inhibited by knockdown of Stat6 but not Stat3 in NHEKs. Moreover, we performed Gal‐7 knockdown experiment on 3D‐reconstructed epidermis and the result suggested that endogenous Gal‐7 serves as a protector from IL‐4/IL‐13–induced disruption of cell‐to‐cell adhesion and/or cell‐to‐extracellular matrix adhesion.Conclusion and Clinical RelevanceOur study unveils the characteristic of Gal‐7 and its possible role as an alarmin that reflects the IL‐4/IL‐13–induced skin barrier impairment in AD.