YTHDF2 contributes to psoriasis by promoting proliferation and inflammatory response through regulation of Wnt signaling pathway

YT521-B homology domain family 2 (YTHDF2), an m6A-binding protein, plays a crucial role in various biological processes, including cell migration, proliferation, differentiation, and inflammation. It is also involved in mRNA decay and pre-rRNA processing. This study investigates the specific impact of YTHDF2 on the pathogenesis of psoriasis and its underlying mechanisms. Initially, increased expression of YTHDF2 was observed in psoriasis. Subsequent silencing of YTHDF2 in psoriatic cell model led to a decrease in mRNA expression of IL-17A, S100A8, and S100A9, as well as a reduction in cell proliferation. Conversely, overexpression of YTHDF2 resulted in the opposite effects. Treatment with the YTHDF2 inhibitor DC-Y27-13 demonstrated a therapeutic effect on psoriasis mice. mRNA sequencing analysis revealed enrichment of differentially expressed genes in the Wnt signaling pathway. Further investigation indicated that deletion of YTHDF2 increased the half-life and expression of Dickkopf homolog 3 (DKK3), which in turn inhibited the Wnt signaling pathway, ultimately attenuating the inflammatory response and inhibiting cell proliferation.