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学科主题: 临床医学
题名:
Knockdown of Filaggrin Impairs Diffusion Barrier Function and Increases UV Sensitivity in a Human Skin Model
作者: Mildner, Michael1; Jin, Jiang1,2; Eckhart, Leopold1; Kezic, Sanja3; Gruber, Florian1; Barresi, Caterina1; Stremnitzer, Caroline1; Buchberger, Maria1; Mlitz, Veronika1; Ballaun, Claudia1; Sterniczky, Barbara1; Foedinger, Dagmar1; Tschachler, Erwin1,4
刊名: JOURNAL OF INVESTIGATIVE DERMATOLOGY
发表日期: 2010-09-01
DOI: 10.1038/jid.2010.115
卷: 130, 期:9, 页:2286-2294
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Dermatology
研究领域[WOS]: Dermatology
关键词[WOS]: N-TERMINAL DOMAIN ; STRATUM-CORNEUM ; ICHTHYOSIS VULGARIS ; ATOPIC-DERMATITIS ; EPIDERMAL DIFFERENTIATION ; HUMAN KERATINOCYTES ; CORNIFIED ENVELOPE ; HUMAN PROFILAGGRIN ; LIPID-COMPOSITION ; UROCANIC ACID
英文摘要:

Loss-of-function mutations in the filaggrin gene are associated with ichthyosis vulgaris and atopic dermatitis. To investigate the impact of filaggrin deficiency on the skin barrier, filaggrin expression was knocked down by small interfering RNA (siRNA) technology in an organotypic skin model in vitro. Three different siRNAs each efficiently suppressed the expression of profilaggrin and the formation of mature filaggrin. Electron microscopy revealed that keratohyalin granules were reduced in number and size and lamellar body formation was disturbed. Expression of keratinocyte differentiation markers and the composition of lipids appeared normal in filaggrin-deficient models. The absence of filaggrin did not render keratins 1, 2, and 10 more susceptible to extraction by urea, arguing against a defect in aggregation. Despite grossly normal stratum corneum morphology, filaggrin-deficient skin models showed a disturbed diffusion barrier function in a dye penetration assay. Moreover, lack of filaggrin led to a reduction in the concentration of urocanic acid, and sensitized the organotypic skin to UVB-induced apoptosis. This study thus demonstrates that knockdown of filaggrin expression in an organotypic skin model reproduces epidermal alterations caused by filaggrin mutations in vivo. In addition, our results challenge the role of filaggrin in intermediate filament aggregation and establish a link between filaggrin and endogenous UVB protection.

语种: 英语
项目资助者: European Union
WOS记录号: WOS:000280912100017
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57384
Appears in Collections:北京大学第二临床医学院_皮科_期刊论文

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作者单位: 1.Med Univ Vienna, Dept Dermatol, A-1090 Vienna, Austria
2.Peking Univ, Dept Dermatol, Peoples Hosp, Beijing 100871, Peoples R China
3.Univ Amsterdam, Acad Med Ctr, Coronel Inst Occupat Hlth, NL-1105 AZ Amsterdam, Netherlands
4.Ctr Rech & Invest Epiderm & Sensorielles, Neuilly, France

Recommended Citation:
Mildner, Michael,Jin, Jiang,Eckhart, Leopold,et al. Knockdown of Filaggrin Impairs Diffusion Barrier Function and Increases UV Sensitivity in a Human Skin Model[J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY,2010,130(9):2286-2294.
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