Dysfunctional Gastric Emptying With Down-regulation of Muscle-Specific MicroRNAs in Helicobacter pylori-Infected Mice
Dysfunctional Gastric Emptying With Down-regulation of Muscle-Specific MicroRNAs in Helicobacter pylori-Infected Mice
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DOI：
10.1053/j.gastro.2010.08.044
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发表时间：
2011-01-01
期刊：
影响因子：
29.4
通讯作者：
Hibi, Toshifumi
中科院分区：
文献类型：
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作者：
Saito, Yoshimasa;Suzuki, Hidekazu;Hibi, Toshifumi
背景与目的：对于功能性消化不良的致病机制知之甚少。我们研究了 microRNA (miRNA) 在与幽门螺杆菌感染相关的胃动力障碍中的作用。方法：雄性C57BL/6小鼠感染幽门螺杆菌。长期感染后，检查胃排空并与未感染小鼠（对照组）进行比较。通过miRNA微阵列和定量逆转录酶聚合酶链反应分析miRNA表达谱。动物研究的结果得到了体外实验的证实。结果：慢性感染幽门螺杆菌后，小鼠的胃排空明显加速。组织学检查显示，感染幽门螺杆菌的小鼠胃部肌肉层明显增厚。 miRNA 表达谱显示，长期感染幽门螺杆菌后，胃中肌肉特异性 miRNA miR-1 和 miR-133 显着下调。然而，据报道 miR-1 和 miR-133 的靶基因组蛋白脱乙酰酶 4 和血清反应因子的表达增加。与幽门螺杆菌共培养后，C2C12 小鼠成肌细胞中观察到 miR-1 和 miR-133 下调，细胞增殖增加。结论：慢性幽门螺杆菌感染会下调肌肉特异性 miRNA 的表达，上调组蛋白脱乙酰酶 4 和血清反应因子的表达。这些可能会导致胃肌层增生和胃排空功能障碍。这些发现提供了对胃动力障碍（包括功能性消化不良）的分子发病机制的深入了解。
BACKGROUND & AIMS: Little is known about the pathogenic mechanisms of functional dyspepsia. We investigated the role of microRNAs (miRNAs) in gastric motility disorders associated with Helicobacter pylori infection. METHODS: Male C57BL/6 mice were infected with H pylori. After long-term infection, gastric emptying was examined and compared with that of uninfected mice (controls). The miRNA expression profile was analyzed by miRNA microarray and quantitative reverse-transcriptase polymerase chain reaction. The results obtained from the animal study were confirmed by in vitro experiments. RESULTS: Gastric emptying was significantly accelerated in mice after chronic infection with H pylori. Histologic examination showed that the muscular layers of the stomachs of H pylori-infected mice were significantly thickened. The miRNA expression profile revealed that the muscle-specific miRNAs miR-1 and miR-133 were significantly down-regulated in the stomachs after long-term infection with H pylori. However, expression of histone deacetylase 4 and serum response factor, which are reported target genes of miR-1 and miR-133, increased. Down-regulation of miR-1 and miR-133 and increased cell proliferation were observed in C2C12 mouse myoblast cells after coculture with H pylori. CONCLUSIONS: Chronic infection with H pylori down-regulates expression of muscle-specific miRNAs and up-regulates expression of histone deacetylase 4 and serum response factor. These might cause hyperplasia in the muscular layer of the stomach and dysfunction in gastric emptying. These findings provide insight into the molecular pathogenesis of gastric motility disorders, including functional dyspepsia.