Persistent JunB activation in fibroblasts disrupts stem cell niche interactions enforcing skin aging
| Autor: | Wilhelm Bloch, Stefan Kochanek, Linda Krug, Peter Angel, Karmveer Singh, Meinhard Wlaschek, Anita Ignatius, Karin Scharffetter-Kochanek, A. Koroma, Pallab Maity, Marina Schorpp-Kistner, Hartmut Geiger, Adelheid Hainzl |
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| Rok vydání: | 2021 |
| Předmět: |
Senescence
JUNB Connective tissue Cell Communication Biology General Biochemistry Genetics and Molecular Biology Collagen Type I Skin Aging Downregulation and upregulation Superoxides medicine Animals Insulin-Like Growth Factor I Stem Cell Niche Fibroblast Transcription factor Cells Cultured Cellular Senescence Cyclin-Dependent Kinase Inhibitor p16 Skin Mice Knockout Superoxide Dismutase Stem Cells Fibroblasts Cell biology medicine.anatomical_structure Stem cell Transcription Factors |
| Zdroj: | Cell reports. 36(9) |
| ISSN: | 2211-1247 |
| Popis: | Fibroblasts residing in the connective tissues constitute the stem cell niche, particularly in organs such as skin. Although the effect of fibroblasts on stem cell niches and organ aging is an emerging concept, the underlying mechanisms are largely unresolved. We report a mechanism of redox-dependent activation of transcription factor JunB, which, through concomitant upregulation of p16INK4A and repression of insulin growth factor-1 (IGF-1), initiates the installment of fibroblast senescence. Fibroblast senescence profoundly disrupts the metabolic and structural niche, and its essential interactions with different stem cells thus enforces depletion of stem cells pools and skin tissue decline. In fact, silencing of JunB in a fibroblast-niche-specific manner-by reinstatement of IGF-1 and p16 levels-restores skin stem cell pools and overall skin tissue integrity. Here, we report a role of JunB in the control of connective tissue niche and identified targets to combat skin aging and associated pathologies. |
| Databáze: | OpenAIRE |
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