ArticlePloS one2012
Transcript profiling identifies dynamic gene expression patterns and an important role for Nrf2/Keap1 pathway in the developing mouse esophagus.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks.BMC cancer · 2017Pooled it
- Targeting notch signaling pathway in esophageal cancer: from molecular insights to therapies.Oncology reviews · 2026Review
- The PI3K pathway is a downstream effector of NRF2 activation in the esophagus.Translational oncology · 2026Article
- Biomarkers of NRF2 signalling: Current status and future challenges.Redox biology · 2024Review
- The KEAP1-NRF2 System and Esophageal Cancer.Cancers · 2022Review
- PAX9 in Cancer Development.International journal of molecular sciences · 2022Review
- Development of targeted therapy of NRF2Cellular signalling · 2021Review
- GPR109A alleviate mastitis and enhances the blood milk barrier by activating AMPK/Nrf2 and autophagy.International journal of biological sciences · 2021Article
- NOTCH and Esophageal Squamous Cell Carcinoma.Advances in experimental medicine and biology · 2021Review
- NRF2/ACSS2 axis mediates the metabolic effect of alcohol drinking on esophageal squamous cell carcinoma.The Biochemical journal · 2020Article
- Hyperactivity of the transcription factor Nrf2 causes metabolic reprogramming in mouse esophagus.The Journal of biological chemistry · 2019Article
- Targeted therapy of esophageal squamous cell carcinoma: the NRF2 signaling pathway as target.Annals of the New York Academy of Sciences · 2018Review
- Esophageal Organoids from Human Pluripotent Stem Cells Delineate Sox2 Functions during Esophageal Specification.Cell stem cell · 2018Article
- PAX9 regulates squamous cell differentiation and carcinogenesis in the oro-oesophageal epithelium.The Journal of pathology · 2018Article
- Nrf2 regulates cellular behaviors and Notch signaling in oral squamous cell carcinoma cells.Biochemical and biophysical research communications · 2017Article
- A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells.Oncotarget · 2016Article
- Chemoprevention of oxidative stress-associated oral carcinogenesis by sulforaphane depends on NRF2 and the isothiocyanate moiety.Oncotarget · 2016Article
- NRF2 Regulates HER2 and HER3 Signaling Pathway to Modulate Sensitivity to Targeted Immunotherapies.Oxidative medicine and cellular longevity · 2016Article
- BMP-driven NRF2 activation in esophageal basal cell differentiation and eosinophilic esophagitis.The Journal of clinical investigation · 2015Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsMorphological changes during human and mouse esophageal development have been well characterized. However, changes at the molecular level in the course of esophageal morphogenesis remain unclear. This study aims to globally profile critical genes and signaling pathways during the development of mouse esophagus. By using microarray analysis this study also aims to determine how the Nrf2/Keap1 pathway regulates the morphogenesis of the esophageal epithelium.
methodsGene expression microarrays were used to survey gene expression in the esophagus at three critical phases: specification, metaplasia and maturation. The esophagi were isolated from wild-type, Nrf2(-/-), Keap1(-/-), or Nrf2(-/-)Keap1(-/-) embryos or young adult mice. Array data were statistically analyzed for differentially expressed genes and pathways. Histochemical and immunohistochemical staining were used to verify potential involvement of the Wnt pathway, Pparβ/δ and the PI3K/Akt pathway in the development of esophageal epithelium.
resultsDynamic gene expression patterns accompanied the morphological changes of the developing esophagus at critical phases. Particularly, the Nrf2/Keap1 pathway had a baseline activity in the metaplasia phase and was further activated in the maturation phase. The Wnt pathway was active early and became inactive later in the metaplasia phase. In addition, Keap1(-/-) mice showed increased expression of Nrf2 downstream targets and genes involved in keratinization. Microarray and immunostaining data also suggested that esophageal hyperkeratosis in the Keap1(-/-) mice was due to activation of Pparβ/δ and the PI3K/Akt pathway.
conclusionsMorphological changes of the esophageal epithelium are associated with dynamic changes in gene expression. Nrf2/Keap1 pathway activity is required for maturation of mouse esophageal epithelium.
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