KLF5 promotes HpSlyD induced gastric intestinal metaplasia by activating Wnt/β-catenin pathway
- Author:
- No author available
- Journal Title:
- World Chinese Journal of Digestology
- Issue:
- 6
- DOI:
- 10.11569/wcjd.v29.i6.274
- Key Word:
- KLF5;Wnt通路;HpSlyD;胃黏膜肠化生
Abstract： 背景Krüppel样因子5(krüppel-like factor 5,KLF5)和Wnt/β-Catenin通路都是肿瘤发生的研究热点,目前有研究发现KLF5与肠上皮细胞的分化和增殖有关,推测其可能参与了肠化生的发生.但目前有关KLF5对胃黏膜肠化生组织增殖、凋亡的影响及其分子机制的研究报道相对较少.目的分析KLF5通过激活Wnt通路对幽门螺杆菌(Helicobacterpylon,Hpylon)诱导胃黏膜肠化生(gastric intestinal metaplasia,GN)作用的影响.方法收集肠化生组织和正常胃黏膜,采用RT-PCR法、Western blot法分别检测KLF5、Wnt3a mRNA和蛋白表达.体外培养胃黏膜上皮细胞GES1,分为空白对照组、HpSlyD组(200 ng/mL的HpSlyD+阴性序列)、干扰LF5组(200 ng/mL的HpSlyD +KLF5 siRNA)、Wnt激动剂组(200 ng/mL的HpSlyD +KLF5 siRNA+氯化锂)、Wnt激动剂+干扰KLF5组.采用MTT法、流式细胞仪分别检测各组GES1细胞增殖、凋亡情况,采用RT-PCR法检测KLF5、Wnt3a、β-catenin、Villin 1,VIL1)、三叶因子Ⅱ(trefoil factor2,TFF2)、尾侧同源盒因子2(caudal homeobox factor 2CDX2)mRNA表达.Western blot法检测VIL1、TFF2、CDX2蛋白表达.结果KLF5、Wnt3a mRNA和蛋白表达量在肠化生组织中明显高于在正常胃黏膜中的表达(P＜0.01).HpSlyD组、干扰对照组细胞增殖率明显高于空白对照组、凋亡率明显低于空白对照组(P＜0.05),干扰KLF5组细胞增殖率明显低于HpSlyD组、凋亡率明显高于HpSlyD组(P＜0.05).HpSlyD组、干扰对照组细胞VIL1、TFF2、CDX2 mRNA和蛋白表达明显高于空白对照组(P＜0.05),干扰KLF5组细胞VIL1、TFF2、CDX2 mRNA和蛋白表达明显低于HpSlyD组(P＜0.05).干扰KLF5组细胞Wnt3a、β-catenin、CDX2mRNA表达明显低于HpSlyD组P＜0.05).而Wnt激动剂+干扰KLF5组Wnt3a、β-catenin、CDX2 mRNA表达明显高于干扰LF5组(P＜0.05).结论干扰KLF5表达可显著抑制HpSlyD诱导的胃黏膜化生的发生,KLF5可能通过激活Wnt/β-Catenin促进HpSlyD诱导的胃黏膜化生,为胃癌的临床预防提供了新的靶点.
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