AZGP1的O-GlcNA酰化调节糖尿病牙周炎中M1/M2巨噬细胞的极化
O-GlcNAcylation of AZGP1 regulates M1/M2 macrophage polarization in diabetic periodontitis.
摘要(中文译文)
牙周炎中巨噬细胞稳态被破坏，而糖尿病常加重这一状况。AZGP1是一种能够调节巨噬细胞极化的炎症相关因子。高血糖会改变病理状态下的O-GlcNAc糖基化动态。本研究探讨了AZGP1在糖尿病牙周炎期间对巨噬细胞极化的调控作用，并探究O-GlcNAc糖基化是否介导了这一效应。将Raw264.7细胞分别暴露于脂多糖（LPS）和高糖（HG）环境，以模拟牙周炎和高血糖微环境。通过qRT-PCR和免疫荧光定量M1和M2标志物来分析巨噬细胞极化。采用免疫沉淀、免疫印迹和放线菌酮追踪实验检测由OGT调控的AZGP1的O-GlcNAc糖基化。建立高血糖牙周炎小鼠模型，评估骨相关参数和巨噬细胞极化。牙龈卟啉单胞菌LPS诱导Raw264.7细胞M1极化并抑制M2极化，而HG进一步放大了LPS驱动的极化。LPS/HG处理后，AZGP1表达升高；敲低AZGP1可抑制M1极化并增强M2极化。敲低OGT通过阻断色氨酸（T205）残基处的O-GlcNAc糖基化降低AZGP1蛋白稳定性。过表达AZGP1可抵消OGT敲低所致的M1/M2极化抑制。在体内，敲低AZGP1通过促进M1向M2极化，减轻高血糖牙周炎小鼠的牙槽骨破坏。由OGT介导的AZGP1 O-GlcNAc糖基化增强其稳定性，在高血糖条件下促进M1极化并抑制M2极化，从而加重高血糖条件下牙周炎的进展。这些发现为糖尿病牙周炎的发病机制和治疗策略提供了新的见解。
Abstract
Macrophage homeostasis is disrupted in periodontitis, a condition often exacerbated by diabetes. AZGP1 is an inflammation-associated factor capable of modulating macrophage polarization. Hyperglycemia alters O-GlcNAcylation dynamics in pathological contexts. This study investigated the regulatory role of AZGP1 in macrophage polarization during diabetic periodontitis and explored whether O-GlcNAcylation mediated this effect. Raw264.7 cells were exposed to lipopolysaccharide (LPS) and high glucose (HG) to simulate the periodontitis and hyperglycemia microenvironment, respectively. Macrophage polarization was analyzed by quantifying M1 and M2 markers via qRT-PCR and immunofluorescence. O-GlcNAcylation of AZGP1 regulated by OGT was examined using immunoprecipitation, immunoblotting, and cycloheximide-chase assays. A hyperglycemic periodontitis mouse model was established, and bone-related parameters and macrophage polarization were assessed. Porphyromonas gingivalis LPS induced M1 polarization and suppressed M2 polarization in Raw264.7 cells, while HG further amplified LPS-driven polarization. Following LPS/HG treatment, AZGP1 expression increased; its knockdown inhibited M1 polarization and enhanced M2 polarization. OGT depletion reduced AZGP1 protein stability by blocking O-GlcNAcylation at the tryptophan (T205) residue. AZGP1 overexpression counteracted the M1/M2 polarization inhibition caused by OGT knockdown. In vivo, AZGP1 knockdown mitigated alveolar bone destruction in periodontitis mice with hyperglycemia by promoting M1 to M2 polarization. O-GlcNAcylation of AZGP1, mediated by OGT, enhances its stability, promoting M1 polarization and suppressing M2 polarization under hyperglycemic conditions, thereby exacerbating periodontitis progression under hyperglycemic conditions. These findings offer novel insights into the pathogenesis and therapeutic strategies for diabetic periodontitis.
如何引用
AMA
Xiaofang Zeng, Hong Xia, Yulong Ma. O-GlcNAcylation of AZGP1 regulates M1/M2 macrophage polarization in diabetic periodontitis.. Odontology. 2026; doi:10.1007/s10266-026-01387-3.
APA
Xiaofang Zeng, Hong Xia, Yulong Ma (2026). O-GlcNAcylation of AZGP1 regulates M1/M2 macrophage polarization in diabetic periodontitis.. Odontology. https://doi.org/10.1007/s10266-026-01387-3
GB/T 7714
Xiaofang Zeng, Hong Xia, Yulong Ma. O-GlcNAcylation of AZGP1 regulates M1/M2 macrophage polarization in diabetic periodontitis.[J]. Odontology, 2026 doi:10.1007/s10266-026-01387-3.
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