Inflammation dependent mTORC1 signaling interferes with the switch from keratinocyte proliferation to differentiation
- Psoriasis is a frequent and often severe inflammatory skin disease, characterized by altered epidermal homeostasis. Since we found previously that Akt/mTOR signaling is hyperactivated in psoriatic skin, we aimed at elucidating the role of aberrant mTORC1 signaling in this disease. We found that under healthy conditions mTOR signaling was shut off when keratinocytes switch from proliferation to terminal differentiation. Inflammatory cytokines (IL-1β, IL-17A, TNF-α) induced aberrant mTOR activity which led to enhanced proliferation and reduced expression of differentiation markers. Conversely, regular differentiation could be restored if mTORC1 signaling was blocked. In mice, activation of mTOR through the agonist MHY1485 also led to aberrant epidermal organization and involucrin distribution. In summary, these results not only identify mTORC1 as an important signal integrator pivotal for the cells fate to either proliferate or differentiate, but emphasize the role of inflammation-dependent mTOR activation as a psoriatic pathomechanism.
Author: | Claudia BürgerORCiDGND, Nitesh Shirsath, Victoria Lang, Alina Berard, Sandra DiehlORCiD, Roland KaufmannGND, Wolf-Henning BoehnckeORCiDGND, Peter Wolf |
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URN: | urn:nbn:de:hebis:30:3-439901 |
DOI: | https://doi.org/10.1371/journal.pone.0180853 |
ISSN: | 1932-6203 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/28700632 |
Parent Title (English): | PLoS one |
Publisher: | PLoS |
Place of publication: | Lawrence, Kan. |
Contributor(s): | Miroslav Blumenberg |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2017/07/24 |
Date of first Publication: | 2017/07/10 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2017/07/24 |
Volume: | 12 |
Issue: | (7): e0180853 |
Page Number: | 20 |
First Page: | 1 |
Last Page: | 20 |
Note: | Copyright: © 2017 Buerger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
HeBIS-PPN: | 416499538 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |