Τίτλος:
Polycystin-1 downregulation induces ERK-dependent mTOR pathway activation in a cellular model of psoriasis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Psoriatic plaques tend to localize to the knees and elbows, areas that are particularly subject to mechanical stress resulting from bending and friction. Moreover, plaques often develop at sites of mechanical trauma or injury (Koebner phenomenon). Nevertheless, mechanotransduction has never been linked to psoriasis. Polycystins (polycystin-1, PC1; polycystin-2, PC2) are mechanosensitive molecules that function as key regulators of cellular mechanosensitivity and mechanotransduction. The aim of this in vitro study was to investigate the role of polycystins in the development of psoriasis. We showed that PC1 knockdown in HaCaT cells led to an elevated mRNA expression of psoriasis-related biomarkers Ki-67, IL-6, TNF-α VEGF and Bcl-2, while PC1 functional inhibition was accompanied by increased cell proliferation and migration of HaCaT cells. In addition, PC1 knockdown via siRNA in HaCaT cells was followed by activation of critical molecules of the mTOR and MAPK pathways and this mTOR pathway activation was ERK-dependent. Furthermore, loss of PC1 protein expression and elevated levels of activated mTOR substrates were also observed in human samples of psoriatic plaques. Overall, our study suggests that the PC1/ERK/mTOR signaling axis represents a novel potential mechanism in psoriasis pathogenesis. © 2018 Elsevier B.V.
Συγγραφείς:
Gargalionis, A.N.
Malakou, L.S.
Adamopoulos, C.
Piperi, C.
Theohari, I.
Nokhbehsaim, M.
Deschner, J.
Kokkalis, G.
Korkolopoulou, P.
Papadavid, E.
Papavassiliou, A.G.
Basdra, E.K.
Περιοδικό:
Biochimica et Biophysica Acta. Molecular Basis of Disease
Λέξεις-κλειδιά:
biological marker; interleukin 6; Ki 67 antigen; mammalian target of rapamycin; messenger RNA; mitogen activated protein kinase; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; polycystin 1; polycystin 2; protein bcl 2; S6 kinase; small interfering RNA; tumor necrosis factor; vasculotropin; MTOR protein, human; polycystic kidney disease 1 protein; polycystin; target of rapamycin kinase, adult; aged; angiogenesis; apoptosis; Article; cell migration assay; cell proliferation; cell proliferation assay; controlled study; Dermatology Life Quality Index; down regulation; friction; gene expression; HaCat cell line; human; human cell; human tissue; immunohistochemistry; in vitro study; keratinocyte; mechanical stress; mechanotransduction; mTOR signaling; MTT assay; pathogenesis; priority journal; protein expression; psoriasis; psoriasis vulgaris; upregulation; biological model; cell line; cell motion; gene knockdown; genetic marker; genetics; MAPK signaling; metabolism; psoriasis, Cell Line; Cell Movement; Cell Proliferation; Down-Regulation; Gene Knockdown Techniques; Genetic Markers; Humans; MAP Kinase Signaling System; Models, Biological; Psoriasis; TOR Serine-Threonine Kinases; TRPP Cation Channels
DOI:
10.1016/j.bbadis.2018.07.036
