FOXC1 ameliorates the disease progression of psoriasis through transcriptional upregulation of SOCS3.

Abstract

Psoriasis is a chronic inflammatory skin disease, and Forkhead box C1 (FOXC1) has been shown to display inhibitory effects on both inflammation and oxidative stress. However, the exact role and underlying mechanism of FOXC1 in the context of psoriasis are yet to be fully explored and clarified. In this study, imiquimod (IMQ) induced experimental psoriasis in mice, and M5-induced keratinocytes (HaCaT) were used to examine the effect of FOXC1 in psoriasis. FOXC1 is downregulated in IMQ-induced mice and M5-treated HaCat cells. Upon overexpressing FOXC1, IMQ-induced psoriasiform skin lesions in mice were improved. Specifically, upregulating FOXC1 in IMQ mice resulted in a reduction in the concentrations of key inflammatory cytokines, including S100A8, S100A9, TNF-α, IL-1β, IL-6, and IL-17 A, effectively alleviating the inflammatory response. Moreover, FOXC1 overexpression exhibited a beneficial effect on oxidative stress, decreased ROS generation, reduced MDA content, and restored the activity of SOD in the skin lesions of psoriasis mice. Similar results were obtained when examining the effect of FOXC1 in M5-induced HaCaT cells. Further investigations suggested that the suppressor of cytokine signaling 3 (SOCS3) might be involved in this process. FOXC1 was found to transcriptionally upregulate the expression of SOCS3 in HaCaT cells. In M5-induced HaCaT cells, the inhibition of SOCS3 reversed the protective effect caused by FOXC1 overexpression, upregulated the expression of S100A8 and S100A9, and promoted ROS levels. Therefore, our findings reveal that the upregulation of FOXC1 ameliorates the disease progression of psoriasis.