Tanaka Shingo, Nagashima Hiroyuki, Uotani Takahiro, Graham David Y, Yamaoka Yoshio
Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA.
Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.
Helicobacter. 2017 Jun;22(3). doi: 10.1111/hel.12376. Epub 2017 Jan 23.
In vitro studies have shown that Helicobacter pylori (H. pylori) infection induces autophagy in gastric epithelial cells. However, prolonged exposure to H. pylori reduces autophagy by preventing maturation of the autolysosome. The alterations of the autophagy-related genes in H. pylori infection are not yet fully understood.
We analyzed autophagy-related gene expression in H. pylori-infected gastric mucosa compared with uninfected gastric mucosa obtained from 136 Bhutanese volunteers with mild dyspeptic symptoms. We also studied single nucleotide polymorphisms (SNPs) of autophagy-related gene in 283 Bhutanese participants to identify the influence on susceptibility to H. pylori infection.
Microarray analysis of 226 autophagy-related genes showed that 16 genes were upregulated (7%) and nine were downregulated (4%). We used quantitative reverse transcriptase polymerase chain reaction to measure mRNA levels of the downregulated genes (ATG16L1, ATG5, ATG4D, and ATG9A) that were core molecules of autophagy. ATG16L1 and ATG5 mRNA levels in H. pylori-positive specimens (n=86) were significantly less than those in H. pylori-negative specimens (n=50). ATG16L1 mRNA levels were inversely related to H. pylori density. We also compared SNPs of ATG16L1 (rs2241880) among 206 H. pylori-positive and 77 H. pylori-negative subjects. The odds ratio for the presence of H. pylori in the GG genotype was 0.40 (95% CI: 0.18-0.91) relative to the AA/AG genotypes.
Autophagy-related gene expression profiling using high-throughput microarray analysis indicated that downregulation of core autophagy machinery genes may depress autophagy functions and possibly provide a better intracellular habit for H. pylori in gastric epithelial cells.
体外研究表明，幽门螺杆菌（H. pylori）感染可诱导胃上皮细胞自噬。然而，长时间暴露于幽门螺杆菌会通过阻止自噬溶酶体成熟来降低自噬。幽门螺杆菌感染中自噬相关基因的改变尚未完全明确。
我们分析了136名有轻度消化不良症状的不丹志愿者的幽门螺杆菌感染胃黏膜与未感染胃黏膜中自噬相关基因的表达。我们还研究了283名不丹参与者自噬相关基因的单核苷酸多态性（SNP），以确定其对幽门螺杆菌感染易感性的影响。
对226个自噬相关基因的微阵列分析显示，16个基因上调（7%），9个基因下调（4%）。我们使用定量逆转录聚合酶链反应来测量下调基因（ATG16L1、ATG5、ATG4D和ATG9A）的mRNA水平，这些基因是自噬的核心分子。幽门螺杆菌阳性标本（n = 86）中的ATG16L1和ATG5 mRNA水平显著低于幽门螺杆菌阴性标本（n = 50）。ATG16L1 mRNA水平与幽门螺杆菌密度呈负相关。我们还比较了206名幽门螺杆菌阳性和77名幽门螺杆菌阴性受试者中ATG16L1（rs2241880）的SNP。相对于AA/AG基因型，GG基因型中幽门螺杆菌存在的比值比为0.40（95% CI：0.18 - 0.91）。
使用高通量微阵列分析的自噬相关基因表达谱表明，核心自噬机制基因的下调可能会抑制自噬功能，并可能为幽门螺杆菌在胃上皮细胞中提供更好的细胞内生存环境。
