國家衛生研究院 NHRI:Item 3990099045/9249
English  |  正體中文  |  简体中文  |  全文笔数/总笔数 : 12145/12927 (94%)
造访人次 : 852376      在线人数 : 1572
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜寻范围 查询小技巧：
  • 您可在西文检索词汇前后加上"双引号"，以获取较精准的检索结果
  • 若欲以作者姓名搜寻，建议至进阶搜寻限定作者字段，可获得较完整数据
    •  进阶搜寻
    主页 ‧ 登入 ‧ 上传 ‧ 说明 ‧ 关于NHRI ‧ 管理 到手机版


    jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/9249


    题名: Inducible expression of gasdermin A3 in the epidermis causes skin inflammation and hair cycle defect
    作者: Lin, H;Lin, P;Yang, L
    贡献者: Institute of Cellular and Systems Medicine
    摘要: The epidermis provides a critical barrier, which is maintained by the epidermal keratinocytes undergoing constant turnover. Gene mutations which disrupt keratincoyte proliferation, differentiation, and death are responsible for skin diseases. Gasdermin A (GSDMA) is expressed in epithelial cells of the upper gastrointestinal tract, lung, and skin; it is involved in apoptosis of the gastric epithelium cells and has been linked with asthma susceptibility in genetic association studies. The function of GSDMA in the skin remains unclear and could only be deduced from autosomal dominant mutations in gasdermin A3 (Gsdma3), an ortholog of GSDMA in mice, which caused progressive epidermal hyperplasia and alopecia. To test the hypothesis that autosomal dominance of Gsdma3 mutations are resulted from Gsdma3 gain-of-function, we generated a doxycycline-inducible double transgenic (DTg) mouse model to express GSDMA3 in the basal keratinocytes using KRT14-rtTA mouse line. We found that induced expression of Gsdma3 caused epidermal hyperplasia, inflammatory infiltrations, and hair cycle defect after depilation, which were associated with increased expression of TNF-α and IL-1α in the epidermis. These skin phenotypes are similar to those reported in Gsdma3 mutant mice. Moreover, necrotic keratinocytes and increased TUNEL-positive staining were found in the DTg epidermis. In primary keratinocytes isolated from the DTg epidermis, induced expression of Gsdma3 caused spontaneous necrosis and leakage of intracellular components with no evidence of autophagy, apoptosis, and endoplasmic reticulum stress. Our data suggest that the dominant mutations in Gsdma3 are gain-of-function mutations, and that an innate immune-mediated mechanism underlies the skin inflammation phenotype of Gsdma3 mutant strains.
    日期: 2015-09
    關聯: Journal of Investigative Dermatology. 2015 Sep;135(Suppl. 2):S56.
    Link to: http://www.nature.com/jid/journal/v135/n2s/full/jid2015271a.html
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-202X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000359739400322
    显示于类别:[楊良棟] 會議論文/會議摘要

    文件中的档案:

    档案 描述 大小格式浏览次数
    ISI000359739400322.pdf62KbAdobe PDF842检视/开启


    在NHRI中所有的数据项都受到原著作权保护.

    TAIR相关文章

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回馈