Epidermal Nbn deletion causes premature hair loss and a phenotype resembling psoriasiform dermatitis.
Oncotarget
; 7(17): 23006-18, 2016 Apr 26.
Article
em En
| MEDLINE
| ID: mdl-27050272
ABSTRACT
Nijmegen 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Psoríase
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Proteínas Nucleares
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Proteína Supressora de Tumor p53
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Proteínas de Ciclo Celular
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Dermatite
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Epiderme
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Alopecia
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article