Epidermal Nbn deletion causes premature hair loss and a phenotype resembling psoriasiform dermatitis
| Autor: | Pierre Olivier Frappart, Amir Abdollahi, Lucien Frappart, Paulius Grigaravicius, Michael Delacher, Martina Remus, Markus Feuerer, Philipp Seidel, Andreas von Deimling, David E. Reuss |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
skin Inflammation Cell Cycle Proteins Dermatitis Neuropathology 03 medical and health sciences Mice 0302 clinical medicine Research Paper: Gerotarget (Focus on Aging) Psoriasis Nbn medicine Animals Psoriasiform Dermatitis inflammation Gerotarget psoriasiform dermatitis Mice Knockout business.industry Cancer Nuclear Proteins Alopecia Hair follicle medicine.disease DNA-Binding Proteins 030104 developmental biology medicine.anatomical_structure Hair loss Phenotype Oncology 030220 oncology & carcinogenesis Immunology medicine.symptom Epidermis Tumor Suppressor Protein p53 business Nijmegen breakage syndrome |
| Zdroj: | Oncotarget OncoTarget, 7:23006-23018 |
| ISSN: | 1949-2553 |
| Popis: | // Philipp Seidel 1,2 , Martina Remus 3 , Michael Delacher 4 , Paulius Grigaravicius 3 , David E. Reuss 5 , Lucien Frappart 6 , Andreas von Deimling 3,5 , Markus Feuerer 4 , Amir Abdollahi 1,2 and Pierre-Olivier Frappart 3 1 Molecular and Translational Radiation Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Medical School (HUMS), Heidelberg, Germany 2 German Cancer Consortium (DKTK) and Heidelberg Institute of Radiation Oncology (HIRO), German Cancer Research Center (DKFZ), Heidelberg, Germany 3 Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany 4 Helmholtz Young Investigator Group Immune Tolerance, Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany 5 Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universitat Heidelberg, Heidelberg, Germany 6 Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Jena, Germany Correspondence to: Pierre-Olivier Frappart, email: // Keywords : inflammation, Nbn, psoriasiform dermatitis, skin, Gerotarget Received : February 17, 2016 Accepted : March 22, 2016 Published : March 30, 2016 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 p16 Ink4a 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. |
| Databáze: | OpenAIRE |
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