Department of Obstetrics and Gynecology, Hebei Medical University, Shijiazhuang 050017, China.
Department of Obstetrics and Gynecology, Bethune International Peace Hospital, Shijiazhuang 050082, Hebei, China.
Aging (Albany NY). 2024 Feb 26;16(4):3790-3802. doi: 10.18632/aging.205560.
To explore the effect of MUC1 on recurrent implantation failure (RIF) and its molecular mechanism.
Bioinformation analysis was used to find possible molecular mechanisms of specific genes in the pathogenesis of RIF. The number of M1 and M2 macrophages was measured by flow cytometry. Immunohistochemical staining and western blotting were used to detect the expression of related proteins. Angiogenesis capacity was measured by cell tube-formation assay.
Bioinformatics analysis results suggest that MUC1 may play an important role in RIF. The results of flow cytometry showed that compared with NC group, M1 macrophages increased significantly and M2 macrophages decreased significantly in MUC1 OE group. The results of immunohistochemical staining showed that MUC1 could inhibit the expression of VEGF. Western blotting results showed that MUC1 could significantly increase the expression of P22, P47, gp91, p-TBK1, IFNγ and IL-1β, and decrease the expression of p-SHP2, p-PI3K, p-mTOR, HIF1α and VEGF. After the addition of ROS inhibitor and PI3K inhibitor, the effect of MUC1 on the above proteins was eliminated. The results of tube formation experiments showed that MUC1 could inhibit vascular formation.
As a promising biomarker for the diagnosis of RIF, MUC1 can promote RIF by regulating macrophage ROS-SHP2 signaling pathway to up-regulate inflammatory response and inhibit angiogenesis.
探讨 MUC1 对反复种植失败（RIF）的影响及其分子机制。
采用生物信息学分析寻找 RIF 发病机制中特定基因的可能分子机制。采用流式细胞术检测 M1 和 M2 巨噬细胞数量。免疫组织化学染色和 Western blot 检测相关蛋白表达。通过细胞管形成实验检测血管生成能力。
生物信息学分析结果提示 MUC1 可能在 RIF 中发挥重要作用。流式细胞术结果显示，与 NC 组相比，MUC1 OE 组 M1 巨噬细胞显著增加，M2 巨噬细胞显著减少。免疫组织化学染色结果显示，MUC1 可抑制 VEGF 的表达。Western blot 结果显示，MUC1 可显著增加 P22、P47、gp91、p-TBK1、IFNγ和 IL-1β的表达，降低 p-SHP2、p-PI3K、p-mTOR、HIF1α和 VEGF 的表达。加入 ROS 抑制剂和 PI3K 抑制剂后，MUC1 对上述蛋白的作用被消除。管形成实验结果表明，MUC1 可抑制血管形成。
作为 RIF 诊断的有前途的生物标志物，MUC1 可通过调节巨噬细胞 ROS-SHP2 信号通路促进 RIF，上调炎症反应并抑制血管生成。
