Polycystin-1 downregulation induces ERK-dependent mTOR pathway activation in a cellular model of psoriasis
| Autor: | Marjan Nokhbehsaim, Penelope Korkolopoulou, Irene Theohari, James Deschner, Efthimia K. Basdra, Antonios N. Gargalionis, Christos Adamopoulos, Christina Piperi, Evangelia Papadavid, Georgios Kokkalis, Lina S. Malakou, Athanasios G. Papavassiliou |
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| Rok vydání: | 2018 |
| Předmět: |
Genetic Markers
0301 basic medicine MAPK/ERK pathway endocrine system TRPP Cation Channels MAP Kinase Signaling System Down-Regulation Models Biological Cell Line 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Movement Psoriasis medicine Humans Mechanotransduction Molecular Biology PI3K/AKT/mTOR pathway Cell Proliferation Gene knockdown Cell growth Chemistry TOR Serine-Threonine Kinases medicine.disease Cell biology HaCaT 030104 developmental biology Gene Knockdown Techniques 030220 oncology & carcinogenesis Molecular Medicine |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1864:3468-3476 |
| ISSN: | 0925-4439 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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