Psoriatic dermal-derived mesenchymal stem cells reduce keratinocyte junctions, and increase glycolysis

Abstract

Although it is known that psoriatic dermal-derived mesenchymal stem cells (DMSCs) dysregulate kera-tinocyte proliferation, the biological activity profile of keratinocytes influenced by psoriatic DMSCs remain unknown. In the present study, we assessed the impact of psoriatic DMSCs on keratinocyte proliferation, differentiation, and glucose metabolism in normal human epidermal keratinocytes co-cultured with or without psoriatic DMSCs. Co-culture of normal human epidermal keratinocytes with psoriatic DMSCs down-regulated expression levels of proteins associated with cell junction assembly (alpha-actinin-1, catenin beta-1, poliovirus receptor-related protein 4 and procolla-gen-lysine, 2-oxoglutarate 5-dioxygenase 2), while upregulating proteins associated with keratinocyte proliferation and differentiation (involucrin, isoform 2 of Histone-binding protein, isoform 3 of Telomeric repeat-binding factor 2 and keratin 13). Moreover, co-culture of normal human epidermal keratinocytes with psoriatic DMSCs stimulated keratinocyte proliferation and glycolysis, but reduced keratinocyte junctions. Ta-ken together, these results demonstrate that psoriatic DMSCs increase keratinocyte proliferation and glycoly-sis, and reduce cell junctions, suggesting a pathogenic role of psoriatic DMSCs in epidermal hyperplasia, aber-rant differentiation, and reduction in turnover time of keratinocytes in psoriasis.