O-linked β-N-acetylglucosamine transferase regulates macrophage polarization in diabetic periodontitis: In vivo and in vitro study

作者：Yeke Wu, Min Liu, Hongling Zhou, Xiang He, Jing Wei, Weihan Hua, Hui‐Jing Li, Qianghua Yuan, Yunfei Xie · 发表于：World Journal of Diabetes · 年份：2025 · DOI：10.4239/wjd.v16.i3.95092 · 被引用次数：6 · 研究领域：Oral microbiology and periodontitis research、Glycosylation and Glycoproteins Research、Immune cells in cancer

BACKGROUND Periodontitis, when exacerbated by diabetes, is characterized by increased M1 macrophage polarization and decreased M2 polarization. O-linked β-N-acetylglucosamine (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), promotes inflammatory responses in diabetic periodontitis (DP). Additionally, p38 mitogen-activated protein kinase regulates macrophage polarization. However, the interplay between OGT, macrophage polarization, and p38 signaling in the progression of DP remains unexplored. AIM To investigate the effect of OGT on macrophage polarization in DP and its role in mediating O-GlcNAcylation of p38. METHODS For in vivo experiments, mice were divided into four groups: Control, DP model, model + short hairpin (sh) RNA-negative control, and model + sh-OGT. Diabetes was induced by streptozotocin, followed by ligation and lipopolysaccharide (LPS) administration to induce periodontitis. The impact of OGT was assessed by injecting sh-OGT lentivirus. Maxillary bone destruction was evaluated using micro-computed tomography analysis and tartrate-resistant acid phosphatase staining, while macrophage polarization was determined through quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry. For in vitro experiments, RAW264.7 cells were treated with LPS and high glucose (HG) (25 mmol/L D-glucose) to establish a cell model of DP. OGT was inhibited by OGT inhibitor (OSMI4) treatment and knocked down by sh-OGT transfection. M1/M2 polarization w...