BackgroundThis study aimed to evaluate the role of fibulin‐3 (FBLN3) in macrophage polarization, its mechanism, and its effect on periodontitis.MethodsWe conducted studies on periodontitis using both clinical samples and ligature‐induced mouse periodontitis model. The inflammatory state was assessed using microcomputed tomography, hematoxylin and eosin staining, immunohistochemical staining, and immunofluorescence staining. In vitro, bone marrow‐derived macrophages, and RAW 264.7 macrophages were treated with lipopolysaccharide (LPS) and interleukin (IL)‐4 to induce polarization. The role of FBLN3 in macrophage polarization was investigated using overexpression plasmids or siRNAs. Furthermore, local injection of adeno‐associated virus was employed to suppress FBLN3 expression in periodontal tissues.ResultsFBLN3 levels were greater in periodontitis tissues. FBLN3 promoted M1 polarization and suppressed M2 polarization in macrophages. The overexpression of FBLN3 promoted M1 polarization via the EGFR/PI3K/AKT signaling pathway, an effect that the epidermal growth factor receptor (EGFR) inhibitor PD153035 reversed. Suppressing FBLN3 expression improved periodontal inflammation and reduced alveolar bone loss in periodontitis.ConclusionsFBLN3 suppression can mitigate periodontitis by decreasing the M1 macrophage ratio. FBLN3 regulates M1 macrophage polarization through the EGFR/PI3K/AKT signaling pathway.Plain language summaryDisruption in the collaboration between extracellular matrix (ECM) and immune system is a significant pathology in periodontitis. Macrophages are a crucial part of the immune system and have unique functions, such as polarization. Fibulin‐3, an ECM protein, may play a vital role in this dynamic interplay. Fibulin‐3 expression is elevated in periodontitis and is closely related to immune cell function. Inhibiting fibulin‐3 can alleviate periodontitis by reducing infiltration of immune cells and M1 macrophage ratio. Furthermore, fibulin‐3 promoted macrophage M1 polarization by activating the PI3K/AKT signaling pathway through EGFR binding. Our findings offer a clinically relevant rationale for immune response modulation through fibulin‐3.

中文翻译：

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抑制腓蛋白-3 通过 EGFR/PI3K/AKT 通路减少 M1 巨噬细胞极化，从而改善牙周炎


背景本研究旨在评估腓蛋白-3 （FBLN3） 在巨噬细胞极化中的作用、其机制及其对牙周炎的影响。方法我们使用临床样本和结扎诱导的小鼠牙周炎模型对牙周炎进行了研究。使用显微计算机断层扫描、苏木精和伊红染色、免疫组化染色和免疫荧光染色评估炎症状态。在体外，用脂多糖 （LPS） 和白细胞介素 （IL）-4 处理骨髓来源的巨噬细胞和 RAW 264.7 巨噬细胞以诱导极化。使用过表达质粒或 siRNA 研究 FBLN3 在巨噬细胞极化中的作用。此外，采用腺相关病毒的局部注射来抑制牙周组织中 FBLN3 的表达。结果牙周炎组织中 FBLN3 水平较高。FBLN3 促进巨噬细胞 M1 极化并抑制 M2 极化。FBLN3 的过表达通过 EGFR/PI3K/AKT 信号通路促进 M1 极化，表皮生长因子受体 （EGFR） 抑制剂PD153035逆转这种效应。抑制 FBLN3 表达可改善牙周炎的牙周炎并减少牙槽骨丢失。结论FBLN3 抑制可通过降低 M1 巨噬细胞比值来减轻牙周炎。FBLN3 通过 EGFR/PI3K/AKT 信号通路调节 M1 巨噬细胞极化。通俗易懂的语言摘要细胞外基质 （ECM） 和免疫系统之间合作的中断是牙周炎的一个重要病理。巨噬细胞是免疫系统的重要组成部分，具有独特的功能，例如极化。Fibulin-3 是一种 ECM 蛋白，可能在这种动态相互作用中起着至关重要的作用。 Fibulin-3 表达在牙周炎中升高，与免疫细胞功能密切相关。抑制腓蛋白-3 可以通过减少免疫细胞的浸润和 M1 巨噬细胞比率来缓解牙周炎。此外，fibulin-3 通过 EGFR 结合激活 PI3K/AKT 信号通路，促进巨噬细胞 M1 极化。我们的研究结果为通过 fibulin-3 调节免疫反应提供了临床相关的基本原理。