Transient receptor potential vanilloid 4 (TRPV4) silencing in Helicobacter pylori‐infected human gastric epithelium. Issue 2 (30th September 2016)

• Record Type: Journal Article
• Authors: Mihara, Hiroshi; Suzuki, Nobuhiro; Muhammad, Jibran Sualeh; Nanjo, Sohachi; Ando, Takayuki; Fujinami, Haruka; Kajiura, Shinya; Hosokawa, Ayumu; Sugiyama, Toshiro
• Is Part Of: Helicobacter. Volume 22:Issue 2(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2016-09-30
• Subjects: gastric epithelium -- Helicobacter pylori -- methylation silencing -- transient receptor potential vanilloid 4 -- TRPV4; Helicobacter -- Periodicals; Helicobacter infections -- Periodicals; Stomach -- Diseases -- Periodicals; 616.3301405
• DOI: 10.1111/hel.12361
• Languages: English
• ISSNs: 1083-4389

Abstract

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. Ca 2+ 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.