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Mammalian target of rapamycin and its downstream signalling components are activated in psoriatic skin
Author(s) -
Buerger C.,
Malisiewicz B.,
Eiser A.,
Hardt K.,
Boehncke W.H.
Publication year - 2013
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.12271
Subject(s) - psoriasis , pi3k/akt/mtor pathway , ribosomal protein s6 , hedgehog signaling pathway , rptor , epidermis (zoology) , phosphorylation , signalling , cancer research , biology , microbiology and biotechnology , kinase , immunohistochemistry , mechanistic target of rapamycin , signal transduction , p70 s6 kinase 1 , immunology , anatomy
Summary Background Mammalian target of rapamycin (m TOR ) signalling integrates signals leading to cellular growth, proliferation and differentiation. Disturbance of this tightly regulated interplay leads to malignancies, as reflected by altered m TOR signalling in epidermal tumours. As psoriatic keratinocytes also show features of perturbed cell growth and differentiation, the question arises as to whether m TOR signalling also plays a role in the pathogenesis of psoriasis. Objectives To investigate the activation status of m TOR signalling components in psoriasis. Methods Biopsies from lesional and nonlesional skin of patients with psoriasis ( n = 10), as well as samples from healthy donors ( n = 3), were analysed by immunohistochemistry and Western blot, utilizing antibodies detecting phosphorylated m TOR , phospho‐ S 6 kinase and phospho‐ S 6 ribosomal protein. Results We found m TOR and its downstream signalling molecule, the ribosomal protein S 6, to be activated in lesional psoriatic skin. While m TOR is activated throughout the whole epidermis, with particularly strong activation in the basal layer, S 6 is active in suprabasal layers of differentiating keratinocytes. Conclusions Altogether these results suggest a role for m TOR signalling in the epidermal changes leading to the psoriatic phenotype. m TOR inhibition might be a mode of action to explore in developing innovative antipsoriatic drugs.