Evidence map›Paper›PMID 25986942›Full record

ArticleGut2016

In oesophageal squamous cells, nitric oxide causes S-nitrosylation of Akt and blocks SOX2 (sex determining region Y-box 2) expression.

Kiyotaka Asanuma, Xiaofang Huo, Agoston Agoston, Xi Zhang, Chunhua Yu, Edaire Cheng, Qiuyang Zhang, Kerry B Dunbar, Thai H Pham, David H Wang and 5 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gut, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Article
  3. Mechanisms and pathophysiology of Barrett oesophagus.Nature reviews. Gastroenterology & hepatology · 2022
    Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. From Reflux Esophagitis to Esophageal Adenocarcinoma.Digestive diseases (Basel, Switzerland)
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 2 countries.

Kiyotaka AsanumaEsophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA Departments of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Xiaofang HuoEsophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA Departments of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Agoston AgostonDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Xi ZhangEsophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA Departments of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Chunhua YuEsophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA Departments of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Edaire ChengEsophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA Department of Pediatrics, Children's Medical Center and the University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Qiuyang ZhangEsophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA Departments of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Kerry B DunbarEsophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA Departments of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Thai H PhamEsophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA Department of Surgery, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA.
David H WangEsophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA Departments of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Katsunori IijimaDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Tooru ShimosegawaDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Robert D OdzeDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Stuart J SpechlerEsophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA Departments of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Rhonda F SouzaEsophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA Departments of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Southwestern Medical Center · USVA North Texas Health Care System · USTohoku University · JPBrigham and Women's Hospital · USHarvard University · USThe University of Texas Southwestern Medical Center · US

Funding

Role of Acid in the Development of Barrett's EsophagusR01DK063621 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI SOUZA, RHONDA F, SPECHLER, STUART JON · 2002 to 2015
$3.4M
ANTECEDANTS SEQUELAE OF CHILDHOOD ONSET DISEASEK12HD068369 · NICHD · UT SOUTHWESTERN MEDICAL CENTER · PI SKAPEK, STEPHEN X · 2011 to 2020
$3.0M
Hedgehog signaling in the development of Barrett's esophagusR01DK097340 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI WANG, DAVID H · 2013 to 2017
$1.4M
Basic and Clinical Studies on the Role of Bile Acids in Barrett's EsophagusR01CA134571 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI SOUZA, RHONDA F, SPECHLER, STUART JON · 2009 to 2013
$1.3M
The Role of Periostin and Th2 Cytokines in Eosinophilic Esophagitis FibrogenesisK08DK099383 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI CHENG, EDAIRE · 2013 to 2016
$595k
Mechanisms of Response to Reflux-Induced Oxidative Stress in Barrett's EsophagusI01BX002666 · VA · VA NORTH TEXAS HEALTH CARE SYSTEM · PI DUNBAR, KERRY BRANDT, SOUZA, RHONDA F · 2015 to 2018
–
BLRD VA I01 BX002666NCI NIH HHS R01 CA134571NICHD NIH HHS K12 HD068369NIDDK NIH HHS K08 DK099383NIDDK NIH HHS R01 DK063621NIDDK NIH HHS R01 DK097340
6 · The paper itself

Abstract

objectiveBarrett's metaplasia might develop if GORD causes oesophageal squamous cells to convert into columnar cells. Acid and bile exposures upregulate columnar differentiation genes like CDX2 in oesophageal squamous cells, but it is not known if such exposures downregulate squamous differentiation genes like SOX2. In addition to acid and bile, patients with GORD also have high oesophageal concentrations of nitric oxide (NO). This study aims to determine how acid, bile salts and NO affect genes that influence oesophageal cell phenotype.

designOesophageal squamous cells from patients with Barrett's oesophagus were exposed to acidic bile salts or NOC-9 (an NO donor). SOX2, p63 (squamous transcription factor) and CDX2 mRNAs were measured by quantitative RT-PCR. SOX2 and its regulatory Akt pathway proteins were evaluated by western blotting. S-nitrosylation by NO was blocked by dithiothreitol. Immunohistochemistry for SOX2 was performed on the oesophagus of rats with surgically induced GORD which were fed diets with and without nitrite supplementation.

resultsIn oesophageal squamous cells, NO profoundly decreased SOX2 protein and caused a significantly greater decrease in SOX2 mRNA than did acidic bile salts. NO also decreased p63 and increased CDX2 expression. NO caused S-nitrosylation of Akt, blocking its phosphorylation. Akt pathway inhibition by LY294002 or Akt siRNA reduced SOX2 mRNA. Rats fed with nitrite-supplemented diets exhibited weaker SOX2 oesophageal staining than rats fed with normal diets.

conclusionsIn oesophageal squamous cells, NO blocks SOX2 expression through Akt S-nitrosylation. NO also increases CDX2 and decreases p63 expression. By triggering molecular events preventing squamous differentiation while promoting intestinal differentiation, NO might contribute to Barrett's pathogenesis.

Indexed as

Barrett EsophagusEpithelial CellsGastroesophageal RefluxAnimalsBile Acids and SaltsCDX2 Transcription FactorCell DifferentiationCell LineDisease Models, AnimalEsophagusHumansMaleNitric OxideRatsRNA, MessengerSignal TransductionBile Acids and SaltsCDX2 protein, humanCDX2 Transcription FactorNitric OxideNOC 9RNA, MessengerSOX2 protein, humanSOXB1 Transcription FactorsTriazenesBARRETT'S METAPLASIAGASTROESOPHAGEAL REFLUX DISEASENITRIC OXIDE

Identifiers

PMID25986942
PMCPMC4651671
OpenAlexW2258718818

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.