Changes in Proteome of Fibroblasts Isolated from Psoriatic Skin Lesions

Abstract

The dermal fibroblasts are in constant contact with the cells of the immune system and skin epidermis. Therefore, they are essential for the development of lesions in psoriasis. The aim of this study was to assess the changes in the proteomic profile of fibroblasts in the dermis of psoriasis patients, and to discuss the most significant changes and their potential consequences. The proteomic results indicate that fibroblast dysfunction arises from the upregulation of proinflammatory factors and antioxidant proteins, as well as those involved in signal transduction and participating in proteolytic processes. Moreover, downregulated proteins in psoriatic fibroblasts are mainly responsible for the transcription/translation processes, glycolysis/ adenosine triphosphate synthesis and structural molecules. These changes can directly affect intercellular signaling and promote the hyperproliferation of epidermal cells. A better understanding of the metabolic effects of the proteomic changes observed could guide the development of new pharmacotherapies for psoriasis.

Keywords: inflammation; intracellular signal transduction; oxidative conditions; proteomic profile; psoriasis; skin fibroblasts.

Figure 1

Venn diagram showing the number of proteins in fibroblasts isolated from the skin of psoriatic patients (n = 5) and healthy controls (n = 5). The names and ID of all the proteins identified are contained in the Supplementary Table S1.

Figure 2

Principal component analysis (PCA) of the proteins in fibroblasts isolated from skin of psoriatic patients (n = 5) and healthy controls (n = 5).

Figure 3

Volcano plot of fibroblasts proteins isolated from the skin of psoriatic patients (n = 5) and healthy controls (n = 5). Red dots indicate proteins of statistical significance among the groups tested. The p-values and the fold change (FC) for each protein are included in Supplementary Table S2.

Figure 4

Heat map and clustering of the 50 most significantly changing proteins of fibroblasts isolated from the skin of psoriatic patients (n = 5) and healthy controls (n = 5).

Figure 5

The level of significantly changed proteins involved in the antioxidant response (A) and inflammation (B) of fibroblasts isolated from skin of psoriatic patients (n = 5) and healthy controls (n = 5).

Figure 6

The level of significantly changed proteins involved in signal transduction/phosphorylation (A), intracellular transport (B) and proteolysis (C) of fibroblasts isolated from the skin of psoriatic patients (n = 5) and healthy controls (n = 5).