KLF11 alleviates rheumatoid arthritis by regulating M1 macrophage polarization via downregulation of YAP1 expression.

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The Gene Expression Omnibus (GEO) datasets (GSE55235 and GSE10500) revealed that KLF11 expression was lower in the patients with RA, which was confirmed by the collected RA samples. However, KLF11's function and molecular mechanism in RA remain to be elucidated. In our study, we investigated this issue using in vivo and in vitro models. Our findings consistently demonstrated the downregulation of KLF11 in mice with collagen-induced arthritis (CIA). Overexpression of KLF11 reduced the arthritis severity and the extent of bone destruction in mice with CIA, whereas KLF11 knockdown exerted the opposite effect. Additionally, it was noted to inhibit M1 macrophage polarization and the ERK pathway both in vivo and in vitro. The JASPAR database indicated the potential for KLF11 to bind to the YAP1 promoter region. ChIP and dual-luciferase reporter assays confirmed the binding of KLF11 to the promoter of YAP1. Further experiments demonstrated that KLF11 negatively regulated YAP1 expression in THP-1 cells. YAP1 overexpression partially reversed the KLF11's inhibitory effect on the ERK signaling pathway and M1 macrophage polarization in vitro. 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