COX-2 Gene promoter methylation in patients infected with Helicobacter Pylori

Yosuke Michikawa, Hhiroshi Yasuda, Yoshiyuki Watanabe, Rritsuko Oikawa, Yoshichika Ohishi, Tadateru Maehata, Fumio Itoh

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Cyclooxygenase (COX) plays a critical role in peptic ulcer development. COX-2 contains CpG islands in promoter area, which suggests possible epigenetic mechanisms of gene silencing. We evaluated COX-2 gene promoter methylation levels in the gastric mucosa of patients with various gastric diseases. DNA was extracted from endoscopic biopsy materials collected from the gastric mucosa. The methylation levels of the COX-2 gene promoter were measured quantitatively by using pyrosequencing. COX-2 mRNA expression in Kato III and AGS cells was measured using real-time PCR. COX-2 gene promoter methylation levels were significantly higher in Helicobacter pylori (HP)-positive cases than in HP-negative cases (27.5% vs. 8.1%, respectively, P-, 0.001). COX-2 gene promoter methylation levels in patients in whom HP was successfully eradicated were significantly lower than those in HP-positive cases (18.7% vs. 27.5%, respectively, P, 0.01). We then investigated the effects of COX-2 gene promoter methylation on its mRNA expression in vitro. COX-2 mRNA expression was not observed in Kato III cells, despite the addition of the protein kinase C stimulator α-phorbol 12,13-dibutyrate (PDBu). COX-2 expression was observed after the addition of the demethylating agent 5-Aza-dC and was enhanced by PDBu. HP infection caused a significant increase in the methylation levels of the COX-2 gene promoter in the gastric mucosa. In addition to transcriptional regulation, COX-2 expression is regulated through epigenetic mechanisms.

Original languageEnglish
Pages (from-to)13-19
Number of pages7
JournalClinical Medicine Insights: Gastroenterology
Volume6
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Cyclooxygenase 2
Helicobacter pylori
Methylation
Genes
Gastric Mucosa
Phorbol 12,13-Dibutyrate
Epigenomics
Messenger RNA
Stomach Diseases
CpG Islands
Helicobacter Infections
Gene Silencing
Prostaglandin-Endoperoxide Synthases
Peptic Ulcer
Protein Kinase C
Real-Time Polymerase Chain Reaction
Biopsy

Keywords

  • COX-2
  • Helicobacter pylori
  • Methylation
  • Stomach

ASJC Scopus subject areas

  • Gastroenterology

Cite this

COX-2 Gene promoter methylation in patients infected with Helicobacter Pylori. / Michikawa, Yosuke; Yasuda, Hhiroshi; Watanabe, Yoshiyuki; Oikawa, Rritsuko; Ohishi, Yoshichika; Maehata, Tadateru; Itoh, Fumio.

In: Clinical Medicine Insights: Gastroenterology, Vol. 6, 2013, p. 13-19.

Research output: Contribution to journalArticle

Michikawa, Yosuke ; Yasuda, Hhiroshi ; Watanabe, Yoshiyuki ; Oikawa, Rritsuko ; Ohishi, Yoshichika ; Maehata, Tadateru ; Itoh, Fumio. / COX-2 Gene promoter methylation in patients infected with Helicobacter Pylori. In: Clinical Medicine Insights: Gastroenterology. 2013 ; Vol. 6. pp. 13-19.
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abstract = "Cyclooxygenase (COX) plays a critical role in peptic ulcer development. COX-2 contains CpG islands in promoter area, which suggests possible epigenetic mechanisms of gene silencing. We evaluated COX-2 gene promoter methylation levels in the gastric mucosa of patients with various gastric diseases. DNA was extracted from endoscopic biopsy materials collected from the gastric mucosa. The methylation levels of the COX-2 gene promoter were measured quantitatively by using pyrosequencing. COX-2 mRNA expression in Kato III and AGS cells was measured using real-time PCR. COX-2 gene promoter methylation levels were significantly higher in Helicobacter pylori (HP)-positive cases than in HP-negative cases (27.5{\%} vs. 8.1{\%}, respectively, P-, 0.001). COX-2 gene promoter methylation levels in patients in whom HP was successfully eradicated were significantly lower than those in HP-positive cases (18.7{\%} vs. 27.5{\%}, respectively, P, 0.01). We then investigated the effects of COX-2 gene promoter methylation on its mRNA expression in vitro. COX-2 mRNA expression was not observed in Kato III cells, despite the addition of the protein kinase C stimulator α-phorbol 12,13-dibutyrate (PDBu). COX-2 expression was observed after the addition of the demethylating agent 5-Aza-dC and was enhanced by PDBu. HP infection caused a significant increase in the methylation levels of the COX-2 gene promoter in the gastric mucosa. In addition to transcriptional regulation, COX-2 expression is regulated through epigenetic mechanisms.",
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