Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, 110001, China.
Department of Pathology, Cancer Hospital of China Medical University; Liaoning Cancer Hospital & Institute, Shenyang, 110042, Liaoning Province, China.
Sci Rep. 2017 May 23;7(1):2278. doi: 10.1038/s41598-017-02642-y.
Helicobacter pylori infection is the most important risk factor for gastric intestinal metaplasia (IM). Our previous study demonstrated that infection with H. pylori HpslyD-positive strains associated with IM. To further investigate the signalling pathway involved in HpSlyD-induced IM, CDX2 and VIL1 expressions were determined before and after HpSlyD application. TCTP was knocked down by siRNA or overexpressed by plasmid transfection. An HpSlyD binding protein was used to block HpSlyD's enzymatic activity. The expression of CDX2 and TCTP in gastric diseases was measured by immunohistochemistry. Our results showed HpSlyD induced CDX2 and VIL1 expressions. TCTP protein expression was markedly increased after application of HpSlyD and in an HpSlyD-expressing stable cell line. Downregulation of TCTP protein led to decreased HpSlyD-induced CDX2 and VIL1. Overexpression of TCTP protein improved the expression of CDX2 and VIL1. Co-application of HpSlyD and FK506 led to significant reductions in CDX2, VIL1, and TCTP expression. Immunohistochemistry demonstrated that CDX2 and TCTP expression was higher in HpslyD-positive specimens compared with HpslyD-negative ones. Expression of CDX2 was positively correlated with TCTP in HpslyD-positive cells. Our study is the first to show that HpSlyD induction of CDX2 and VIL1 expression mediated through TCTP may contribute to IM in the stomach.
幽门螺杆菌感染是胃肠化生（IM）最重要的危险因素。我们之前的研究表明，感染 H. pylori HpslyD 阳性菌株与 IM 相关。为了进一步研究 HpSlyD 诱导 IM 涉及的信号通路，在应用 HpSlyD 前后测定了 CDX2 和 VIL1 的表达。TCTP 通过 siRNA 敲低或质粒转染过表达。用 HpSlyD 结合蛋白阻断 HpSlyD 的酶活性。通过免疫组织化学测定胃疾病中 CDX2 和 TCTP 的表达。结果显示 HpSlyD 诱导 CDX2 和 VIL1 的表达。应用 HpSlyD 后和在表达 HpSlyD 的稳定细胞系中，TCTP 蛋白表达明显增加。TCTP 蛋白下调导致 HpSlyD 诱导的 CDX2 和 VIL1 减少。TCTP 蛋白的过表达改善了 CDX2 和 VIL1 的表达。HpSlyD 和 FK506 的共同应用导致 CDX2、VIL1 和 TCTP 表达显著降低。免疫组织化学显示 HpslyD 阳性标本中 CDX2 和 TCTP 的表达高于 HpslyD 阴性标本。HpslyD 阳性细胞中 CDX2 的表达与 TCTP 呈正相关。本研究首次表明，HpSlyD 通过 TCTP 诱导 CDX2 和 VIL1 的表达可能有助于胃 IM 的发生。
