幽门螺杆菌诱导胃靶细胞中 Lgr5 的表达和干细胞特性。
Helicobacter pylori induces the expression of Lgr5 and stem cell properties in gastric target cells.
发表日期：2024 Nov
作者：
Zuzana Nascakova, Jiazhuo He, Giovanni Papa, Biel Francas, Flora Azizi, Anne Müller
来源：
Stem Cell Research & Therapy
摘要：
幽门螺杆菌感染使携带者患胃癌的风险很高。胃窦癌的细胞起源是Lgr5干细胞。在这里，我们发现，通过免疫荧光显微镜、qRT-PCR 和蛋白质印迹法确定，幽门螺杆菌感染胃窦来源的胃类器官细胞会增加干细胞标记物 Lgr5 的表达，无论是当细胞作为单层生长和感染时，还是当细胞暴露于 3D 结构中的幽门螺杆菌时。通过球体形成测定确定，幽门螺杆菌暴露增加了干性特性。 Lgr5 的表达和干性的获得依赖于功能性 IV 型分泌系统 (T4SS)，并且至少部分依赖于 T4SS 效应子 CagA。 NF-κB 的药理抑制或基因消除可逆转 Lgr5 和球体形成的增加。由于 Apc 失活而导致的持续活跃的 Wnt/β-catenin 信号传导加剧了幽门螺杆菌诱导的 Lgr5 表达和干性，这两种情况甚至在感染根除后仍然存在。综合数据表明，幽门螺杆菌具有诱导干性的特性，这取决于其激活 NF-κB 信号传导的能力。© 2024 Nascakova 等人。
Helicobacter pylori infection predisposes carriers to a high risk of developing gastric cancer. The cell-of-origin of antral gastric cancer is the Lgr5+ stem cell. Here, we show that infection of antrum-derived gastric organoid cells with H. pylori increases the expression of the stem cell marker Lgr5 as determined by immunofluorescence microscopy, qRT-PCR, and Western blotting, both when cells are grown and infected as monolayers and when cells are exposed to H. pylori in 3D structures. H. pylori exposure increases stemness properties as determined by spheroid formation assay. Lgr5 expression and the acquisition of stemness depend on a functional type IV secretion system (T4SS) and at least partly on the T4SS effector CagA. The pharmacological inhibition or genetic ablation of NF-κB reverses the increase in Lgr5 and spheroid formation. Constitutively active Wnt/β-catenin signaling because of Apc inactivation exacerbates H. pylori-induced Lgr5 expression and stemness, both of which persist even after eradication of the infection. The combined data indicate that H. pylori has stemness-inducing properties that depend on its ability to activate NF-κB signaling.© 2024 Nascakova et al.