TY  - JOUR
A1  - Bürger, Claudia
A1  - Shirsath, Nitesh
A1  - Lang, Victoria
A1  - Berard, Alina
A1  - Diehl, Sandra
A1  - Kaufmann, Roland
A1  - Boehncke, Wolf-Henning
A1  - Wolf, Peter
T1  - Inflammation dependent mTORC1 signaling interferes with the switch from keratinocyte proliferation to differentiation
T2  - PLoS one
N2  - 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.
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/43990
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-439901
SN  - 1932-6203
N1  - 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.
VL  - 12
IS  - (7): e0180853
SP  - 1
EP  - 20
PB  - PLoS
CY  - Lawrence, Kan.
ER  -