Analysis of epithelial–mesenchymal transition markers in psoriatic epidermal keratinocytes

Abstract

Psoriasis is similar to endpoints of epithelial–mesenchymal transition (EMT), a process of epithelial cells transformed into fibroblast-like cells. The molecular epithelial and mesenchymal markers were analysed in psoriatic keratinocytes. No obvious alteration of epithelial markers E-cadherin (E-cad), keratin 10 (K10), K14 and K16 was detected in psoriatic keratinocytes. However, significantly increased expression of Vim, FN, plasminogen activator inhibitor 1 (PAI-1) and Slug was seen. IL-17A and IL-13 at 50 ng ml−1 strongly decreased expression of K10, Vim and FN. TGF-β1 at 50 ng ml−1 promoted the production of N-cad, Vim, FN and PAI-1. Slug was decreased by dexamethasone (Dex), but E-cad was upregulated by Dex. Silencing of ERK partially increased E-cad and K16, but remarkably inhibited K14, FN, Vim, β-catenin, Slug and α5 integrin. Moreover, inhibition of Rho and GSK3 by their inhibitors Y27632 and SB216763, respectively, strongly raised E-cad, β-catenin and Slug. Dex decreased Y27632-mediated increase of β-catenin. Dex at 2.0 µM inhibited SB216763-regulated E-cad, β-catenin and slug. In conclusion, EMT in psoriatic keratinocytes may be defined as an intermediate phenotype of type 2 EMT. ERK, Rho and GSK3 play active roles in the process of EMT in psoriatic keratinocytes.

Control of fibrotic changes through the synergistic effects of anti-fibronectin antibody and an RGDS-tagged form of the same antibody

“…5D ). In agreement with previous studies 16 17 , inhibitors for ERK and p38 signaling pathways resulted in significant decrease in expression of the EMT markers ( Fig. 5 ).…”

Variances in the mRNA expression profile of TGF-β1–3 isoforms and its TGF-βRI–III receptors during cyclosporin a treatment of psoriatic patients

“…Following phosphorylation of protein and Smad2, they form a complex with Smad4, gather inside the nucleus and act as transcription agents. This cascade of events changes the gene expression in keratinocytes, which inhibits proliferation, increases diversification and susceptibility to apoptosis [ 51 , 52 ].…”

“…It involved considerably reduced quantities of TGF-β1 and IL-6, IL-23 and IL-17A. Managing TGF-β/Smad3 signalling with the use of Smad3 inhibitor may constitute a new and efficient option in psoriasis therapy [ 52 – 54 ].…”

Role of keratin 24 in human epidermal keratinocytes

“…EMT is thought to be remodeling of the cytoskeleton, such as down regulation of epithelial keratins, which leads to alterations in cell-to-cell adhesions and changes in polarity and cell motility[32]. Loss of keratin expression is a hallmark of psoriasis and skin tumors[33, 34], and EMT is believed to support invasiveness of tumors and metastasis formation[35, 36]. In our study, K24 decreased expression of mesenchymal markers such as N-cadherin and slug, whereas it increased epithelial marker E-cadherin.…”