國家衛生研究院 NHRI:Item 3990099045/15282
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    题名: Gasdermin a guards epidermal differentiation and cornification in skin barrier repair: Its role in atopic dermatitis pathogenesis
    作者: Huang, L;Li, S;Lin, S;Kao, C;Hong, C;Lee, C;Yang, L
    贡献者: Institute of Cellular and Systems Medicine
    摘要: Atopic dermatitis (AD) is featured with impaired skin barrier. The stratum corneum (SC) and the intercellular tight junctions (TJs) constitute the permeability barrier, which is essential to protect the host water loss and pathogen entrance. The SC is constantly renewed by differentiating keratinocytes through cornification, during which autophagy contributes to organelles and nucleus elimination. The human GSDMA and its mouse homologs Gsdma1e3 are expressed in the suprabasal epidermis. Although a pyroptotic role for GSDMA/Gsdma1 in host defense against Streptococcus pyogenes has been reported, the physiological function of Gsdma1/a2/a3 in epidermal homeostasis remains elusive. Herein, through repeated epidermal barrier disruption, we found that TJ formation and SC maturation were defective in the Gsdma1/a3-deficient epidermis. Using comparative gene profiling analysis, mitochondrial respiration measurement, and in vivo tracing of mitochondrial turnover, our data indicate that Gsdma1/a3 are required for acute epidermal cornification by inducing mitochondrial dysfunction and ensuing mitophagy. In MC903-induced AD-like animal model, we demonstrated that Gsdma1/a3-deficiency selectively enhanced the Th2 response. Remarkably, the GSDMA expression is reduced in the epidermis of patients with AD compared to normal individuals. Gsdma1/a3-deficiency might be involved in AD pathogenesis, likely through GSDMA-mediated epidermal differentiation and cornification.
    日期: 2023-05
    關聯: Journal of Investigative Dermatology. 2023 May;143(5):S128.
    Link to: https://doi.org/10.1016/j.jid.2023.03.754
    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:001037960300741
    显示于类别:[楊良棟] 會議論文/會議摘要

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