PMID- 31700071
OWN - NLM
STAT- MEDLINE
DCOM- 20201104
LR  - 20210208
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Nov 7
TI  - Effect of Proton Pump Inhibitor Therapy on NOX5, mPGES1 and iNOS expression in 
      Barrett's Esophagus.
PG  - 16242
LID - 10.1038/s41598-019-52800-7 [doi]
LID - 16242
AB  - Acid reflux may contribute to the progression from Barrett's esophagus (BE) to 
      esophageal adenocarcinoma (EA). However, it is not clear whether the molecular 
      changes present in BE patients are reversible after proton pump inhibitor (PPI) 
      treatment. In this study we examined whether PPI treatment affects NOX5, 
      microsomal prostaglandin E synthase (mPGES)-1 and inducible nitric oxide synthase 
      (iNOS) expression. We found that NADPH oxidase 5 (NOX5), mPGES-1 and iNOS were 
      significantly increased in BE mucosa. One-month PPI treatment significantly 
      decreased NOX5, mPGES1 and iNOS. In BAR-T cells, NOX5 mRNA and p16 promoter 
      methylation increased after pulsed acid treatment in a time-dependent manner. 
      Four or eight-week-acid induced increase in NOX5 mRNA, NOX5 protein and p16 
      methylation may be reversible. Twelve-week acid treatment also significantly 
      increased NOX5, mPGES1 and iNOS mRNA expression. However, 
      twelve-week-acid-induced changes only partially restored or did not recover at 
      all after the cells were cultured at pH 7.2 for 8 weeks. We conclude that NOX5, 
      mPGES1 and iNOS may be reversible after PPI treatment. Short-term acid-induced 
      increase in NOX5 expression and p16 methylation might be reversible, whereas 
      long-term acid-induced changes only partially recovered 8 weeks after removal of 
      acid treatment.
FAU - Li, Dan
AU  - Li D
AD  - Department of Medicine, Rhode Island Hospital and Warren Alpert Medical School of 
      Brown University, Providence, RI, 02903, USA.
FAU - Deconda, Deepthi
AU  - Deconda D
AD  - Southcoast Physicians Group, Fall river, MA, 02720, USA.
FAU - Li, Aihua
AU  - Li A
AD  - Department of Medicine, Rhode Island Hospital and Warren Alpert Medical School of 
      Brown University, Providence, RI, 02903, USA.
FAU - Habr, Fadlallah
AU  - Habr F
AD  - Department of Medicine, Rhode Island Hospital and Warren Alpert Medical School of 
      Brown University, Providence, RI, 02903, USA. FHabr@lifespan.org.
FAU - Cao, Weibiao
AU  - Cao W
AD  - Department of Medicine, Rhode Island Hospital and Warren Alpert Medical School of 
      Brown University, Providence, RI, 02903, USA. wcao@hotmail.com.
AD  - Department of Pathology, Rhode Island Hospital and Warren Alpert Medical School 
      of Brown University, Providence, RI, 02903, USA. wcao@hotmail.com.
LA  - eng
GR  - R01 DK080703/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20191107
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (CDKN2A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Proton Pump Inhibitors)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.6.3.- (NADPH Oxidase 5)
RN  - EC 5.3.99.3 (PTGES protein, human)
RN  - EC 5.3.99.3 (Prostaglandin-E Synthases)
SB  - IM
MH  - Aged
MH  - Barrett Esophagus/*drug therapy/*genetics
MH  - Cyclin-Dependent Kinase Inhibitor p16/genetics
MH  - DNA Methylation/drug effects
MH  - Female
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mucous Membrane/drug effects/metabolism
MH  - NADPH Oxidase 5/*genetics
MH  - Nitric Oxide Synthase Type II/*genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Prostaglandin-E Synthases/*genetics
MH  - Proton Pump Inhibitors/*pharmacology/therapeutic use
PMC - PMC6838155
COIS- The authors declare no competing interests.
EDAT- 2019/11/09 06:00
MHDA- 2020/11/05 06:00
PMCR- 2019/11/07
CRDT- 2019/11/09 06:00
PHST- 2019/05/13 00:00 [received]
PHST- 2019/10/10 00:00 [accepted]
PHST- 2019/11/09 06:00 [entrez]
PHST- 2019/11/09 06:00 [pubmed]
PHST- 2020/11/05 06:00 [medline]
PHST- 2019/11/07 00:00 [pmc-release]
AID - 10.1038/s41598-019-52800-7 [pii]
AID - 52800 [pii]
AID - 10.1038/s41598-019-52800-7 [doi]
PST - epublish
SO  - Sci Rep. 2019 Nov 7;9(1):16242. doi: 10.1038/s41598-019-52800-7.