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New therapeutic targets in dermatoporosis

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Published in Journal of Nutrition, Health and Aging. 2012, vol. 16, no. 4, p. 285-8
Abstract Dermatoporosis is a novel term proposed to describe the chronic cutaneous insufficiency/fragility syndrome characterized by an extreme skin atrophy. Dermatoporosis is principally due to chronological aging and long-term and unprotected sun exposure, but it may also result from the chronic use of topical and systemic corticosteroids. We have recently proposed a membrane organelle, hyalurosome, composed of molecules involved in hyaluronate (HA) metabolism and cell signaling in the keratinocytes, such as principal HA receptor CD44, heparin-binding epidermal growth factor (HB-EGF), HB-EGF receptor erbB1 and HA synthase 3 (HAS3), which is functionally defective in dermatoporosis and may be a target for intervention. Several lines of evidence suggest that hyalurosome is located in keratinocyte filopodia, thin, actin-rich plasma membrane protrusions implicated in cell motility. We have recently shown that keratinocyte filopodia are downregulated by corticosteroids in vitro. Intermediate size HA fragments (HAFi) inhibited the downregulation of filopodia induced by corticosteroids. Topical HAFi prevented the skin atrophy induced by topical corticosteroids in mice without interfering with their anti-inflammatory effect. Topical treatment with HAFi 1% of atrophic forearm skin of dermatoporosis patients for 1 month resulted in a significant clinical improvement and induced the expression of hyalurosome molecules. Topical retinaldehyde (RAL) and HAFi showed a synergy in HA production and pro-HB-EGF expression in mouse skin and in the correction of skin atrophy in dermatoporosis patients. Uncovering the molecular mechanisms implicating hyalurosome seems to be crucial to better understand the pathogenesis of dermatoporosis and to develop new therapeutic strategies.
Keywords Adrenal Cortex Hormones/adverse effects/antagonists & inhibitorsAgedAged, 80 and overAgingAnimalsAtrophyCell MovementDown-Regulation/drug effectsDrug SynergismEpidermis/metabolism/pathologyFemaleGlucuronosyltransferase/metabolismHumansHyaluronic Acid/metabolismIntercellular Signaling Peptides and Proteins/metabolismKeratinocytes/cytology/drug effects/metabolismMaleMiceMiddle AgedPseudopodia/metabolismRetinaldehyde/pharmacologySkin/drug effects/pathologySkin Diseases/drug therapy/physiopathology
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PMID: 22499444
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Research group Mécanismes des pathologies de l'inflammation cutanée (919)
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KAYA, Gurkan. New therapeutic targets in dermatoporosis. In: Journal of Nutrition, Health and Aging, 2012, vol. 16, n° 4, p. 285-8. https://archive-ouverte.unige.ch/unige:29921

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Deposited on : 2013-09-25

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