Transient receptor potential vanilloid 4 (TRPV4) silencing in Helicobacter pylori-infected human gastric epithelium

Hiroshi Mihara*, Nobuhiro Suzuki, Jibran Sualeh Muhammad, Sohachi Nanjo, Takayuki Ando, Haruka Fujinami, Shinya Kajiura, Ayumu Hosokawa, Toshiro Sugiyama

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Background: Helicobacter pylori (HP) infection induces methylation silencing of specific genes in gastric epithelium. Various stimuli activate the nonselective cation channel TRPV4, which is expressed in gastric epithelium where it detects mechanical stimuli and promotes ATP release. As CpG islands in TRPV4 are methylated in HP-infected gastric epithelium, we evaluated HP infection-dependent changes in TRPV4 expression in gastric epithelium. Materials and Methods: Human gastric biopsy samples, a human gastric cancer cell line (AGS), and a normal gastric epithelial cell line (GES-1) were used to detect TRPV4 mRNA and protein expression by RT-PCR and Western blotting, respectively. Ca2+ imaging was used to evaluate TRPV4 ion channel activity. TRPV4 methylation status was assessed by methylation-specific PCR (MSP). ATP release was measured by a luciferin-luciferase assay. Results: TRPV4 mRNA and protein were detected in human gastric biopsy samples and in GES-1 cells. MSP and demethylation assays showed TRPV4 methylation silencing in AGS cells. HP coculture directly induced methylation silencing of TRPV4 in GES-1 cells. In human samples, HP infection was associated with TRPV4 methylation silencing that recovered after HP eradication in a time-dependent manner. Conclusion: HP infection-dependent DNA methylation suppressed TRPV4 expression in human gastric epithelia, suggesting that TRPV4 methylation may be involved in HP-associated dyspepsia.

Original languageEnglish
Article numbere12361
JournalHelicobacter
Volume22
Issue number2
DOIs
StatePublished - 2017/04/01

Keywords

  • Gastric epithelium
  • Helicobacter pylori
  • Methylation silencing
  • TRPV4
  • Transient receptor potential vanilloid 4

ASJC Scopus subject areas

  • Gastroenterology
  • Infectious Diseases

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