Gastroenterology:紧密连接蛋白Claudin 18的缺失会促进小鼠胃中肿瘤的形成

2018-12-09 MedSci MedSci原创

有研究表明claudin 18(CLDN18)(一种跨膜紧密连接蛋白)的丢失发生在胃癌发展的早期阶段,并且会导致患者的存活时间较短。因此研究人员试图探究CLDN18的丢失是否发生在由于幽门螺杆菌感染而发生上皮内瘤变和侵袭性腺体的小鼠中,以及它的损失是否会促进幽门螺杆菌感染的小鼠中类似病变的发生。

背景与目的
有研究表明claudin 18(CLDN18)(一种跨膜紧密连接蛋白)的丢失发生在癌发展的早期阶段,并且会导致患者的存活时间较短。因此研究人员试图探究CLDN18的丢失是否发生在由于幽门螺杆菌感染而发生上皮内瘤变和侵袭性腺体的小鼠中,以及它的损失是否会促进幽门螺杆菌感染的小鼠中类似病变的发生。

方法
研究人员对感染幽门螺旋杆菌的6至15个月B6:129小鼠的组织中的CLDN18水平进行免疫组织化学分析。研究人员还分析了具有全长CLDN18基因表达的敲除小鼠和对照小鼠。通过电子显微镜分析来自对照和CLDN18敲除小鼠的组织,通过常规方法染色并分析组织病理学,通过激光捕获显微切割制备并通过RNAseq分析,并对谱系标记,增殖标记和干细胞标记物进行免疫染色。

结果
CLDN18在上皮细胞中具有基底外侧而非顶端紧密连接定位。与未感染幽门螺杆菌的小鼠相比,感染幽门螺杆菌的小鼠胃组织中的CLDN18的水平是增加的,CLDN18首先从大多数胃腺中丢失,然后在胃颈和表面细胞中表达被破坏和减少。CLDN18敲除小鼠的胃组织具有低水平的炎症但增加的细胞增殖,表达肠道增殖性解痉多肽表达化生的标志物。

结论
感染幽门螺杆菌的小鼠在胃癌进展早期降低了CLDN18的表达, CLDN18可以调节小鼠胃中的细胞谱系分化和细胞信号传导。

原始出处:

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    2019-08-30 hb2008ye
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    2019-02-09 许安
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    2018-12-10 kafei

    学习了谢谢

    0