| Epimorphin-derived peptide antagonists remedy epidermal parakeratosis triggered by unsaturated fatty acid. | |
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MedLine Citation:
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PMID: 20688483 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Unsaturated fatty acid from accumulated sebum disrupts calcium influx in keratinocytes and triggers epidermal hyperplasia, leading to comedone formation in the skin. Oleic acid, a representative unsaturated fatty acid, has been shown to be a useful reagent to induce these cellular alternations, however, the detailed mechanism still remains to be elucidated. OBJECTIVES: This study aimed at the identification of the mediator of unsaturated fatty acid-caused epidermal hyperplasia so as to generate the effective therapeutic agents. METHODS: The downstream mediator of oleic acid-treatment was identified in the epidermal keratinocyte and the effect of its antagonistic peptides on the epidermal behaviors was investigated in culture and in vivo. RESULTS: In culture, treatment with oleic acid augmented extracellular secretion of epimorphin in HaCaT keratinocytes and prevented the epidermal terminal differentiation including programmed cell death and cornified envelope formation. The antagonistic peptide of epimorphin (EPn1: a circular compound composed of CGSIEQSC), which was newly generated in this study, restored normal keratinocyte behaviors. In hairless mice, topical application of oleic acid to the dorsal skin caused epidermal hyperplasia with decreased enucleation in the horny layer, which was dramatically hampered by the administration of EPn1. CONCLUSIONS: The effects of unsaturated fatty acid are attributed to the overstimulation of epimorphin signaling and suggest the epimorphin antagonist as a possible therapeutic agent for acne and hyperkeratotic skin disease. |
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Authors:
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Yoji Okugawa; J Jamie Bascom; Yohei Hirai |
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Publication Detail:
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Type: Journal Article Date: 2010-07-15 |
Journal Detail:
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Title: Journal of dermatological science Volume: 59 ISSN: 1873-569X ISO Abbreviation: J. Dermatol. Sci. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-31 Completed Date: 2010-12-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9011485 Medline TA: J Dermatol Sci Country: Netherlands |
Other Details:
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Languages: eng Pagination: 176-83 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Japanese Society for Investigative Dermatology. All rights reserved. |
Affiliation:
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Department of Bioscience, School of Science and Engineering, Kwansei Gakuin University, Sanda 669-1337, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis Cell Culture Techniques Cell Differentiation / drug effects Epidermis / drug effects Female Humans Hyperplasia / drug therapy Keratinocytes / drug effects, metabolism Membrane Glycoproteins / antagonists & inhibitors*, metabolism Mice Mice, Hairless Oleic Acid / adverse effects* Parakeratosis / chemically induced*, drug therapy* Peptides, Cyclic / pharmacology, therapeutic use* |
| Chemical | |
Reg. No./Substance:
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0/EPn1 peptide; 0/Epim protein, mouse; 0/Membrane Glycoproteins; 0/Peptides, Cyclic; 112-80-1/Oleic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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