依赖HtrA的E-Cadherin排泄会损害初级胃上皮细胞和胃器官的上皮屏障功能
Marina Canadas-Ortega1,2, Iris Mühlbacher3, Gernot Posselt1,2,4
1Department of Biosciences and Medical Biology, Division of Microbial Infection and Cancer, Paris-Lodron University of Salzburg, 5020 Salzburg, Austria.
International journal of molecular sciences
|July 13, 2024
概括
杆菌的蛋白酶HtrA在胃细胞中分裂E-cadherin,损害细胞粘附. 这促进了非癌性胃内膜细胞的细菌入侵和致病.
科学领域:
- 微生物学 微生物学
- 细胞生物学 细胞生物学
- 胃肠病学 胃肠病学
背景情况:
- 损坏的E-cadherin (Cdh1) 功能与癌症的进展和转移有关.
- 杆菌 (H. pylori) 感染是胃疾病的主要原因之一.
- 杆菌分泌高温要求的A (HtrA) 蛋白酶,涉及到Cdh1分泌.
研究的目的:
- 为了研究HtrA介导的Cdh1裂变在非新发性胃上皮细胞中.
- 在初级胃模型中确定HtrA对H.pylori病变的影响.
- 评估由HtrA引起的细菌转移和CagA转位.
主要方法:
- 使用了人类原发性上皮细胞系 (胃状细胞,粘膜状细胞).
- 分析了HtrA诱导的Cdh1外皮层裂变.
- 使用显微镜,TEER和cfu测定测量细菌传播.
- 评估了CagA注射和氨酸酸化.
主要成果:
- HtrA严重损害了Cdh1功能,通过2D细胞和粘膜体的外皮层裂变.
- HtrA部分去极化了粘膜单层,促进了细菌的传播.
- 在二维细胞中发生了有效的CagA转位和酸化,在粘膜体中也有类似的效果.
结论:
- HtrA 是 H. pylori 病原发生的一个关键因素.
- 在非转化原性胃上皮细胞和有机体模型中,HtrA促进细菌病原性.
- 通过HtrA介导的Cdh1裂变有助于H. pylori的多阶段病原发生.
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