Polycystin-1 downregulation induces ERK-dependent mTOR pathway activation in a cellular model of psoriasis.

Abstract

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.

• Authors: Antonios N Gargalionis, Lina S Malakou, Christos Adamopoulos, Christina Piperi, Irene Theohari, Marjan Nokhbehsaim, James Deschner, Georgios Kokkalis, Penelope Korkolopoulou, Evangelia Papadavid, Athanasios G Papavassiliou, Efthimia K Basdra
• Journal: Biochimica et biophysica acta. Molecular basis of disease (Biochim Biophys Acta Mol Basis Dis) Vol. 1864 Issue 10 Pg. 3468-3476 (10 2018) ISSN: 1879-260X [Electronic] Netherlands
• PMID: 30077613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Genetic Markers
• TRPP Cation Channels
• polycystic kidney disease 1 protein
• MTOR protein, human
• TOR Serine-Threonine Kinases

Topics

• Cell Line
• Cell Movement
• Cell Proliferation
• Down-Regulation
• Gene Knockdown Techniques
• Genetic Markers
• Humans
• MAP Kinase Signaling System
• Models, Biological
• Psoriasis (genetics, metabolism)
• TOR Serine-Threonine Kinases (metabolism)
• TRPP Cation Channels (genetics, metabolism)