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目的 探讨分化簇53（CD53）通过Janus激酶2（JAK2）/信号转导及转录激活因子3（STAT3）/CD24信号轴在炎症环境下对泡沫细胞胞葬障碍的调控作用及其潜在分子机制。方法 采用巯基乙酸盐肉汤诱导小鼠腹腔巨噬细胞，将其与氧化型低密度脂蛋白共培养48h诱导形成泡沫细胞。将泡沫细胞分为对照1组、联合脂多糖（LPS）/γ干扰素（IFN-γ）1组、LPS/IFN-γ+siCD53组（转染靶向CD53的siRNA沉默CD53），后两组以20ng/mLIFN-γ预处理2h、50ng/mLLPS继续培养24h构建炎症环境，并以0.1μmol/L地塞米松处理16h诱导凋亡。采用实时荧光定量PCR检测CD53及炎症因子白细胞介素1β（IL-1β）、IL-6、肿瘤坏死因子α（TNF-α）、单核细胞趋化蛋白1（MCP-1）mRNA表达；Westernblotting检测CD53、CD24、磷酸化JAK2（p-JAK2）、磷酸化STAT3（p-STAT3）蛋白表达；流式细胞术检测巨噬细胞对凋亡泡沫细胞的胞葬水平。另设对照2组、LPS/IFN-γ2组、LPS/IFN-γ+siCD24组，观察沉默CD24对胞葬水平的影响。结果 与对照1组比较，LPS/IFN-γ1组泡沫细胞CD53mRNA和蛋白表达高（P均<0.05），IL-1β、IL-6、TNF-α、MCP-1mRNA表达高（P均<0.05），胞葬水平低（P<0.05），CD24、p-JAK2、p-STAT3蛋白表达高（P均<0.05）。与LPS/IFN-γ1组比较，LPS/IFN-γ+siCD53组CD53mRNA和蛋白表达低（P均<0.05），炎症因子mRNA表达低（P均<0.05），胞葬水平高（P<0.05），CD24、p-JAK2、p-STAT3蛋白表达低（P均<0.05）。与LPS/IFN-γ2组比较，LPS/IFN-γ+siCD24组胞葬水平高（P<0.05）。结论 炎症环境下泡沫细胞CD53表达上调，沉默CD53可减轻炎症反应并逆转胞葬障碍；其可能通过激活JAK2/STAT3信号通路上调CD24表达，从而抑制胞葬过程。
Abstract：CD53 regulates foam cell efferocytosis impairment through the JAK2/STAT3/CD24 axis in an inflammatory environment Objective To investigate the regulatory role of cluster of differentiation 53 (CD53) via the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3)/CD24 signaling axis in efferocytosis impairment of foam cells under inflammatory conditions and its potential molecular mechanisms. Methods Mouse peritoneal macrophages were induced by thioglycollate broth and co-cultured with oxidized low-density lipoprotein for 48 h to induce foam cell formation. The foam cells were divided into control group 1， lipopolysaccharide (LPS)/interferon-γ (IFN-γ) group 1， and LPS/IFN-γ+siCD53 group (transfected with siRNA targeting CD53 to silence CD53). In the latter two groups， an inflammatory environment was established by pretreatment with 20 ng/mL IFN-γ for 2 h followed by 50 ng/mL LPS for 24 h， and apoptosis was induced by treatment with 0.1 μmol/L dexamethasone for 16 h. Real-time quantitative PCR was used to detect the mRNA expression of CD53 and inflammatory cytokines including interleukin-1β (IL-1β)， IL-6， tumor necrosis factor-α (TNF-α)， and monocyte chemoattractant protein-1 (MCP-1). Western blotting was performed to detect the protein expression of CD53， CD24， phosphorylated JAK2 (p-JAK2)， and phosphorylated STAT3 (p-STAT3). Flow cytometry was used to assess the efferocytosis level of macrophages toward apoptotic foam cells. Additionally， LPS/IFN-γ group 2 and LPS/IFN-γ+siCD24 group were established to observe the effect of CD24 silencing on efferocytosis. Results Compared with control group 1， the LPS/IFN-γ group 1 showed increased mRNA and protein expression of CD53 in foam cells (all P<0.05)， elevated mRNA expression of IL-1β， IL-6， TNF-α， and MCP-1 (all P<0.05)， decreased efferocytosis level (P<0.05)， and upregulated protein expression of CD24， p-JAK2， and p-STAT3 (all P<0.05). Compared with the LPS/IFN-γ group 1， the LPS/IFN-γ+siCD53 group exhibited decreased mRNA and protein expression of CD53 (all P<0.05)， reduced mRNA expression of inflammatory cytokines (all P<0.05)， increased efferocytosis level (P<0.05)， and downregulated protein expression of CD24， p-JAK2， and p-STAT3 (all P<0.05). Compared with the LPS/IFN-γ group 2， the LPS/IFN-γ+siCD24 group showed increased efferocytosis level (P<0.05). Conclusion CD53 expression is upregulated in foam cells under inflammatory conditions， and silencing CD53 alleviates the inflammatory response and reverses efferocytosis impairment， possibly through activating the JAK2/STAT3 signaling pathway to upregulate CD24 expression， thereby inhibiting the efferocytosis process.
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基本信息:
中图分类号:R543.5
引用信息:
[1]胡景堂,王珍,王鹏,等.基于JAK2/STAT3/CD24信号轴探讨CD53调控炎症环境下泡沫细胞胞葬障碍的机制[J].山东医药().
基金信息:
四川省自然科学基金项目（2025ZNSFSC1702）
2026-08-05
2026-08-05
2026-08-05