Regulation of retinoid-mediated signaling in the skin and its implication for skin homeostasis in mice

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dc.contributor.advisorRalph, Rühl
dc.contributor.authorGericke, Janine
dc.contributor.authorvariantGericke, Janine
dc.contributor.departmentMolekuláris sejt- és immunbiológia doktori iskolahu
dc.contributor.submitterdepDE--OEC--Általános Orvostudományi Kar -- DE--OEC--Általános Orvostudományi Kar --
dc.contributor.submitterdepDE--OEC--Általános Orvostudományi Kar --
dc.contributor.submitterdepDE--OEC--Általános Orvostudományi Kar --
dc.contributor.submitterdepDE--OEC--Általános Orvostudományi Kar --
dc.contributor.submitterdepDE--OEC--Általános Orvostudományi Kar --
dc.contributor.submitterdepDE--OEC--Általános Orvostudományi Kar --
dc.date.accessioned2014-01-15T07:29:49Z
dc.date.available2014-01-15T07:29:49Z
dc.date.created2013hu_HU
dc.date.defended2014-02-14
dc.date.issued2014-01-15T07:29:49Z
dc.description.abstractEndogenous retinoids like all-trans retinoic acid (ATRA) play important roles in skin physiology and immune-modulatory events in the skin via nuclear hormone receptor-mediated signaling through RARs and/or RXRs. Moreover, it has been shown recently that ATRA can activate another nuclear receptor involved in skin homeostasis, namely PPARδ, depending on specific transport proteins: Fabp5 initiates PPARδ signaling whereas Crabp2 promotes signaling via RAR. Notably, alterations in retinoid metabolism, signaling, and concentrations have been found in various skin diseases such as atopic dermatitis. Thereby, it remains unclear whether these changes are symptoms or the trigger of such diseases. The aim of this study was to determine how topically applied agonists or antagonists selective for RARs or RXRs and how the induction of an allergic immune response by systemic or combined systemic and topical treatment with ovalbumin influence retinoid metabolism and signaling in mouse skin. Of further interest were nuclear receptor ligand treatment effects on epidermal barrier homeostasis and skin-based immune regulation relevant for skin disorders such as atopic dermatitis, as well as their correlation to the allergen-induced dermatitis mouse model. Our data indicate that RARα and RARγ subtypes possess different roles in mouse skin and may be of relevance for the auto-regulation of endogenous retinoid signaling in the skin. Moreover, dysregulated retinoid signaling mediated by RXR, RARα and/or RARγ as well as potential unidentified pathways may promote skin-based inflammation and disturbance of epidermal barrier properties. This is further supported by elevated ATRA levels and mainly increased signaling mediated by RAR or PPARδ in allergen-induced dermatitis skin. Furthermore, systemic sensitization with an allergen is sufficient to modify the expression of genes central to epidermal homeostasis suggesting an “inside-out” effect of allergen in allergic skin disease pathogenesis possibly by increasing allergen penetration through the skin. In summary, disturbed retinoid metabolism and retinoid-mediated signaling in the skin may contribute to the development and/or maintenance of allergic skin diseases. Whether these alterations are symptoms or potential initiators of atopic sensitization still remains to be elucidated.hu_HU
dc.description.correctorde
dc.format.extent81hu_HU
dc.identifier.urihttp://hdl.handle.net/2437/178550
dc.language.isoenhu_HU
dc.subjectAllergen-induced dermatitishu_HU
dc.subjectall-trans retinoic acid
dc.subjectatopic dermatitis
dc.subjectfatty acid binding protein 5
dc.subjectgene expression
dc.subjectnuclear hormone receptor
dc.subjectperoxisome proliferator-activated receptor δ
dc.subjectretinoic acid receptor
dc.subjectretinoids
dc.subjectretinoid X receptor
dc.subjectskin
dc.subject.disciplineElméleti orvostudományokhu
dc.subject.sciencefieldOrvostudományokhu
dc.titleRegulation of retinoid-mediated signaling in the skin and its implication for skin homeostasis in micehu_HU
dc.title.translatedRetinoid-mediált jelátvitel szabályozása a bőrben és hatása a bőr homeosztázisra egérbenhu_HU
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Molekuláris Sejt- és Immunbiológia Doktori Iskola