Keratinocyte-specific ablation of Mcpip1 impairs skin integrity and promotes local and systemic inflammation
| العنوان: | Keratinocyte-specific ablation of Mcpip1 impairs skin integrity and promotes local and systemic inflammation |
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| المؤلفون: | Agnieszka Paziewska, Agata Lichawska-Cieslar, Patrycja Kwiecińska, Weronika Szukala, Roza Pietrzycka, Joanna Cichy, Michael Devos, Wim Declercq, Luis F. Santamaria-Babí, Jolanta Jura, Izabela Rumienczyk, Mingui Fu, Maria Kulecka, Piotr Konieczny, Michal Mikula, Julia Borowczyk |
| المصدر: | J Mol Med (Berl) Journal of Molecular Medicine |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Keratinocytes, Aging, Systemic inflammation, Mice, 0302 clinical medicine, Drug Discovery, Medicine, Genetics (clinical), Barrier function, Cells, Cultured, Skin, 0303 health sciences, Cell Differentiation, Regnase-1, 3. Good health, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Molecular Medicine, Keratins, medicine.symptom, Keratinocyte, ZC3H12A, Inflammation, Mice, Transgenic, Article, Proinflammatory cytokine, S100A8, 03 medical and health sciences, Ribonucleases, Downregulation and upregulation, Cornified Envelope Proline-Rich Proteins, skin inflammation, Proliferating Cell Nuclear Antigen, Animals, Calgranulin A, 030304 developmental biology, Cell Proliferation, business.industry, MCPIP1, Molecular medicine, Mice, Inbred C57BL, Gene Ontology, Gene Expression Regulation, Lymph Nodes, Epidermis, business, Transcriptome, Spleen, Interleukin-1 |
| الوصف: | MCPIP1 (Regnase-1, encoded by the ZC3H12A gene) regulates the mRNA stability of several inflammatory cytokines. Due to the critical role of this RNA endonuclease in the suppression of inflammation, Mcpip1 deficiency in mice leads to the development of postnatal multiorgan inflammation and premature death. Here, we generated mice with conditional deletion of Mcpip1 in the epidermis (Mcpip1EKO). Mcpip1 loss in keratinocytes resulted in the upregulated expression of transcripts encoding factors related to inflammation and keratinocyte differentiation, such as IL-36α/γ cytokines, S100a8/a9 antibacterial peptides, and Sprr2d/2h proteins. Upon aging, the Mcpip1EKO mice showed impaired skin integrity that led to the progressive development of spontaneous skin pathology and systemic inflammation. Furthermore, we found that the lack of epidermal Mcpip1 expression impaired the balance of keratinocyte proliferation and differentiation. Overall, we provide evidence that keratinocyte-specific Mcpip1 activity is crucial for the maintenance of skin integrity as well as for the prevention of excessive local and systemic inflammation. KEY MESSAGES: Loss of murine epidermal Mcpip1 upregulates transcripts related to inflammation and keratinocyte differentiation. Keratinocyte Mcpip1 function is essential to maintain the integrity of skin in adult mice. Ablation of Mcpip1 in mouse epidermis leads to the development of local and systemic inflammation. |
| تدمد: | 1432-1440 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4dacd79e2b6c3a12891d3eed3e6c6f80 https://pubmed.ncbi.nlm.nih.gov/31786670 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4dacd79e2b6c3a12891d3eed3e6c6f80 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321440 |
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