| Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis. | |
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MedLine Citation:
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PMID: 20004782 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Psoriasis and atopic dermatitis (AD) are common, complex inflammatory skin diseases. Both diseases display immune infiltrates in lesions and epidermal growth/differentiation alterations associated with a defective skin barrier. An incomplete understanding of differences between these diseases makes it difficult to compare human disease pathology to animal disease models. OBJECTIVE: To characterize differences between these diseases in expression of genes related to epidermal growth/differentiation and inflammatory circuits. METHODS: We performed genomic profiling of mRNA in chronic psoriasis (n = 15) and AD (n = 18) skin lesions compared with normal human skin (n = 15). RESULTS: As expected, clear disease classifications could be constructed on the basis of expected immune polarity (T(H)1, T(H)2, T(H)17) differences. However, even more striking differences were identified in epidermal differentiation programs that could be used for precise disease classifications. Although both psoriasis and AD skin lesions displayed regenerative epidermal hyperplasia, which is a general alteration in epidermal growth, keratinocyte terminal differentiation was differentially polarized. In AD, we found selective defects in expression of multiple genes encoding the cornified envelope, with the largest alteration in loricrin (expressed at 2% of the level of normal skin). At the ultrastructural level, the cornified envelope in AD was broadly defective with highly decreased compaction of corneocytes and reduced intercellular lipids. Hence, the entire keratinocyte terminal differentiation program (cytoplasmic compaction, cornification, and lipid release) is defective in AD, potentially underlying the immune differences. CONCLUSION: Our study shows that although alterations in barrier responses exist in both diseases, epidermal differentiation is differentially polarized, with major implications for primary disease pathogenesis. |
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Authors:
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Emma Guttman-Yassky; Mayte Suárez-Fariñas; Andrea Chiricozzi; Kristine E Nograles; Avner Shemer; Judilyn Fuentes-Duculan; Irma Cardinale; Peng Lin; Reuven Bergman; Anne M Bowcock; James G Krueger |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: The Journal of allergy and clinical immunology Volume: 124 ISSN: 1097-6825 ISO Abbreviation: J. Allergy Clin. Immunol. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-16 Completed Date: 2010-01-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1275002 Medline TA: J Allergy Clin Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 1235-1244.e58 Citation Subset: AIM; IM |
Affiliation:
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Laboratory for Investigative Dermatology, Rockefeller University, New York, NY 10065, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Dermatitis, Atopic / genetics*, pathology* Down-Regulation Epidermis / ultrastructure* Female Gene Expression Profiling Humans Male Microscopy, Electron, Transmission Middle Aged Psoriasis / genetics, pathology Up-Regulation Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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5UL1RR024143-02/RR/NCRR NIH HHS |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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