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

Polycystin-1 downregulation induces ERK-dependent mTOR pathway activation in a cellular model of psoriasis. Biochim Biophys Acta. 2018 Aug 02;: Authors: Gargalionis AN, Malakou LS, Adamopoulos C, Piperi C, Theochari I, Nokhbehsaim M, Deschner J, Kokkalis G, Korkolopoulou P, Papadavid E, Papavassiliou AG, Basdra EK 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 wer...
Source: Biochimica et Biophysica Acta - Category: Biochemistry Authors: Tags: Biochim Biophys Acta Source Type: research