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Scientific article
Open access
English

Inflammation dependent mTORC1 signaling interferes with the switch from keratinocyte proliferation to differentiation

Published inPLOS ONE, vol. 12, no. 7, e0180853
Publication date2017
Abstract

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.

Keywords
  • Adolescent
  • Adult
  • Aged
  • Animals
  • Cell Differentiation/genetics/physiology
  • Cell Line
  • Cell Proliferation/genetics/physiology
  • Female
  • Humans
  • Immunoassay
  • Immunohistochemistry
  • Keratinocytes/metabolism/physiology
  • Male
  • Mechanistic Target of Rapamycin Complex 1
  • Mice
  • Mice
  • Inbred BALB C
  • Middle Aged
  • Multiprotein Complexes/genetics/metabolism
  • RNA
  • Small Interfering/genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction/genetics/physiology
  • TOR Serine-Threonine Kinases/genetics/metabolism
  • Young Adult
Citation (ISO format)
BUERGER, Claudia et al. Inflammation dependent mTORC1 signaling interferes with the switch from keratinocyte proliferation to differentiation. In: PLOS ONE, 2017, vol. 12, n° 7, p. e0180853. doi: 10.1371/journal.pone.0180853
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal1932-6203
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179downloads

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