Dysfunctional gastric emptying with down-regulation of muscle-specific microRNAs in Helicobacter pylori-infected mice.
OBJECTIVE
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.
Saito
Yoshimasa
Y
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Suzuki
Hidekazu
H
Tsugawa
Hitoshi
H
Suzuki
Sachiko
S
Matsuzaki
Juntaro
J
Hirata
Kenro
K
Hibi
Toshifumi
T
D000818:Animals; D002908:Chronic Disease; D015536:Down-Regulation; D004415:Dyspepsia / Q000378:metabolism / Q000382:microbiology*; D005746:Gastric Emptying; D005753:Gastric Mucosa / Q000378:metabolism; D020869:Gene Expression Profiling; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori; D006655:Histone Deacetylases / Q000032:analysis / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009130:Muscle, Smooth / Q000378:metabolism*; D026362:Serum Response Factor / Q000032:analysis / Q000378:metabolism; D013270:Stomach / Q000382:microbiology; D013272:Stomach Diseases / Q000378:metabolism / Q000382:microbiology*; D015854:Up-Regulation
D035683:MicroRNAs; D026362:Serum Response Factor; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases