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000130537 1001_ $$aSeidel, Philipp$$b0
000130537 245__ $$aEpidermal Nbn deletion causes premature hair loss and a phenotype resembling psoriasiform dermatitis.
000130537 260__ $$a[S.l.]$$bImpact Journals LLC$$c2016
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000130537 520__ $$aNijmegen Breakage Syndrome is a disease caused by NBN mutations. Here, we report a novel function of Nbn in skin homeostasis. We found that Nbn deficiency in hair follicle (HF) progenitors promoted increased DNA damage signaling, stimulating p16Ink4a up-regulation, Trp53 stabilization and cytokines secretion leading to HF-growth arrest and hair loss. At later stages, the basal keratinocytes layer exhibited also enhanced DNA damage response but in contrast to the one in HF progenitor was not associated with pro-inflammatory cytokines expression, but rather increased proliferation, lack of differentiation and immune response resembling psoriasiform dermatitis. Simultaneous Nbn and Trp53 inactivation significantly exacerbated this phenotype, due to the lack of inhibition of pro-inflammatory cytokines secretion by Trp53. Altogether, we demonstrated novel functions of Nbn in HF maintenance and prevention of skin inflammation and we provide a mechanistic explanation that links cell intrinsic DNA maintenance with large scale morphological tissue alterations.
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000130537 7001_ $$aRemus, Martina$$b1
000130537 7001_ $$0P:(DE-He78)a4340add02b610f9dbdba2dc909cbd09$$aDelacher, Michael$$b2$$udkfz
000130537 7001_ $$0P:(DE-HGF)0$$aGrigaravicius, Paulius$$b3
000130537 7001_ $$aReuss, David E$$b4
000130537 7001_ $$aFrappart, Lucien$$b5
000130537 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b6$$udkfz
000130537 7001_ $$0P:(DE-He78)f0638edf1d3f61c0d7ebb587f511733f$$aFeuerer, Markus$$b7$$udkfz
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000130537 7001_ $$0P:(DE-He78)703947df9988b30a962cc68cd7e8df0a$$aFrappart, Pierre-Olivier$$b9$$eLast author$$udkfz
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