the mechanisms of the generation, maintenance and control of stratum corneum and tight junctions

角质层和紧密连接的生成、维持和控制机制

• 批准号: 22791089
• 负责人: YOKOUCHI Mariko
• 金额: $ 2.58万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22791089/
• 关键词: 重層扁平上皮; 可視化; Tight junction; Tight Junction; 表皮バリア

Mammalian skin consists of two sets of barriers : stratum corneum(SC) and tight junctions(TJs). Filaggrin is a structural protein of SC. The loss-of-function mutations in filaggrin gene are reported as a major predisposing factor for atopic dermatitis, suggesting that disrupted SC barrier might result in increased entry of external antigens. Epidermal TJ also functions as an outside-in barrier, however, TJ barrier function under filaggrin-deficient conditions has not been investigated. In this study, we examined the epidermal TJ structure and functions in filaggrin knockout mice, which completely lack filaggrin expression in the epidermis. 3D structure of epidermal TJ was investigated in a whole-mounted ear epidermis using confocal microscopy. In filaggrin KO mice, the expression and localization of TJ-related proteins were not affected. TJ-permeability assay using a primary amine-reactive biotinylation reagent as a tracer revealed that the barrier function of TJ against water-soluble～ 500 dalton molecule was neither altered in neonatal mouse nor adult mice of these filaggrin-deficient models. These results suggested that the absence of filaggrin does not alter the barrier function of TJ directly.

哺乳动物皮肤由两组屏障组成：角质层（SC）和紧密连接（TJ）。Filaggrin是SC的结构蛋白，Filaggrin基因的功能缺失突变是特应性皮炎的主要易感因素，提示SC屏障的破坏可能导致外部抗原进入增加。表皮TJ也起着由外向内屏障的作用，然而，在丝聚集蛋白缺乏的条件下TJ屏障的功能尚未研究。在这项研究中，我们研究了表皮TJ结构和功能的聚丝蛋白基因敲除小鼠，完全缺乏聚丝蛋白表达的表皮。利用共聚焦显微镜在全贴装的耳表皮中研究了表皮TJ的3D结构。在丝聚蛋白基因敲除小鼠中，TJ相关蛋白的表达和定位不受影响。使用伯胺反应性生物素化试剂作为示踪剂的TJ渗透性测定显示，TJ对水溶性~ 500道尔顿分子的屏障功能在这些丝聚集蛋白缺陷模型的新生小鼠和成年小鼠中均未改变。这些结果表明，聚丝蛋白的缺乏不会直接改变TJ的屏障功能。

项目成果

Investigation of the tight junction barrier in hair follicles and sebaceous glands

毛囊和皮脂腺紧密连接屏障的研究

• 发表时间: 2011
• 作者: Shin'ichi Arakawa;Tetsuya Takine;Masayuki Murata;Yui Sasaki;大石敏之;Kubo A
• 通讯作者: Kubo A

Maintenance of intact epidermal tight junction barriers in filaggrin-deficient mouse models

丝聚蛋白缺陷小鼠模型中完整表皮紧密连接屏障的维持

• 发表时间: 2010
• 作者: Yokouchi M;Kubo A;Kawasaki H;Amagai M
• 通讯作者: Amagai M

Human epidermal tight junctions are functional and allow penetration of activated Langerhans cell dendrites

人类表皮紧密连接具有功能性，可以穿透激活的朗格汉斯细胞树突

• 发表时间: 2011
• 作者: Keisuke Hotta;Yoshiki Higo;and Shinji Kusumoto;春山拓哉・草野修平・永次 史;Yoshida K
• 通讯作者: Yoshida K

Langerin-positive Langerhans cells but not Langerin-negative inflammatory dendritic epidermal cells penetrate epidermal tight junction barriers in atopic dermatitis

在特应性皮炎中，Langerin 阳性朗格汉斯细胞而非 Langerin 阴性炎症树突状表皮细胞穿透表皮紧密连接屏障

• 发表时间: 2011
• 作者: 磯貝明;齋藤継之;Yoshida K
• 通讯作者: Yoshida K

Antigen capture through tight junctions by Langerhans cells confer pre-emptive immunity in experimental staphylococcal scaled skin syndrome

朗格汉斯细胞通过紧密连接捕获抗原，赋予实验性葡萄球菌鳞屑性皮肤综合征先发制人的免疫力

• 发表时间: 2011
• 作者: Yuichi Futa;Hiroyuki Okazaki;Yasunari Shidama;Ouchi T
• 通讯作者: Ouchi T