Liu Xiaodan, Fang Fang, Duan Hongmei, Wu Chunling, Liu Haina, Ding Shuang
Clinical Laboratory Department, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, China.
Department of Rheumatology and Immunology, The First Hospital of China Medical University, No.155, Nanjingbei Street, Heping District, Shenyang , Liaoning Province, 110001, China.
Arthritis Res Ther. 2025 Aug 26;27(1):171. doi: 10.1186/s13075-025-03634-4.
Rheumatoid arthritis (RA) is a chronic autoimmune disease, primarily impacting joints and bones. 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. KLF11 may be a promising therapeutic target for RA.
类风湿关节炎（RA）是一种慢性自身免疫性疾病，主要影响关节和骨骼。基因表达综合数据库（GEO）数据集（GSE55235和GSE10500）显示，RA患者中KLF11的表达较低，这一点在收集的RA样本中得到了证实。然而，KLF11在RA中的功能和分子机制仍有待阐明。在我们的研究中，我们使用体内和体外模型对这个问题进行了研究。我们的研究结果一致表明，在胶原诱导的关节炎（CIA）小鼠中KLF11表达下调。KLF11的过表达降低了CIA小鼠的关节炎严重程度和骨破坏程度，而KLF11基因敲低则产生相反的效果。此外，还发现它在体内和体外均能抑制M1巨噬细胞极化和ERK通路。JASPAR数据库表明KLF11有可能与YAP1启动子区域结合。染色质免疫沉淀（ChIP）和双荧光素酶报告基因检测证实了KLF11与YAP1启动子的结合。进一步的实验表明，KLF11在THP-1细胞中负调控YAP1的表达。YAP1的过表达部分逆转了KLF11在体外对ERK信号通路和M1巨噬细胞极化的抑制作用。KLF11可能是RA一个有前景的治疗靶点。
