Effect of Proton Pump Inhibitor Therapy on NOX5, mPGES1 and iNOS expression in Barrett's Esophagus.
Effect of Proton Pump Inhibitor Therapy on NOX5, mPGES1 and iNOS expression in Barrett's Esophagus.
复制标题
质子泵抑制剂治疗对 Barrett 食管中 NOX5、mPGES1 和 iNOS 表达的影响。
DOI：
10.1038/s41598-019-52800-7
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发表时间：
2019
影响因子：
4.6
通讯作者：
Cao,Weibiao
中科院分区：
文献类型：
--
作者：
Li,Dan;Deconda,Deepthi;Li,Aihua;Habr,Fadlallah;Cao,Weibiao
胃酸反流可能导致巴雷特食管（BE）发展为食管腺癌（EA）。然而，目前尚不清楚质子泵抑制剂（PPI）治疗后BE患者的分子变化是否可逆。在这项研究中，我们检测了PPI治疗是否影响NOX5、微粒体前列腺素E合成酶(mPGES)-1和诱导型一氧化氮合成酶（iNOS）的表达。结果发现，BE粘膜NADPH氧化酶5 （NOX5）、mPGES-1和iNOS显著升高。PPI治疗1个月显著降低NOX5、mPGES1和iNOS。在BAR-T细胞中，脉冲酸处理后，NOX5 mRNA和p16启动子甲基化以时间依赖性的方式增加。4周或8周酸诱导的NOX5 mRNA、NOX5蛋白和p16甲基化的增加可能是可逆的。酸处理12周后，NOX5、mPGES1和iNOS mRNA表达均显著升高。然而，在pH为7.2的条件下培养8周后，12周酸诱导的变化仅部分恢复或根本没有恢复。我们认为NOX5、mPGES1和iNOS在PPI治疗后可能是可逆的。短期酸诱导的NOX5表达和p16甲基化的增加可能是可逆的，而长期酸诱导的变化在去除酸处理后8周仅部分恢复。
Acid reflux may contribute to the progression from Barrett’s esophagus (BE) to esophageal adenocarcinoma (EA). However, it is not clear whether the molecular changes present in BE patients are reversible after proton pump inhibitor (PPI) treatment. In this study we examined whether PPI treatment affects NOX5, microsomal prostaglandin E synthase (mPGES)-1 and inducible nitric oxide synthase (iNOS) expression. We found that NADPH oxidase 5 (NOX5), mPGES-1 and iNOS were significantly increased in BE mucosa. One-month PPI treatment significantly decreased NOX5, mPGES1 and iNOS. In BAR-T cells, NOX5 mRNA and p16 promoter methylation increased after pulsed acid treatment in a time-dependent manner. Four or eight-week-acid induced increase in NOX5 mRNA, NOX5 protein and p16 methylation may be reversible. Twelve-week acid treatment also significantly increased NOX5, mPGES1 and iNOS mRNA expression. However, twelve-week-acid-induced changes only partially restored or did not recover at all after the cells were cultured at pH 7.2 for 8 weeks. We conclude that NOX5, mPGES1 and iNOS may be reversible after PPI treatment. Short-term acid-induced increase in NOX5 expression and p16 methylation might be reversible, whereas long-term acid-induced changes only partially recovered 8 weeks after removal of acid treatment.