scholarly journals Pathogenesis of Barrett's esophagus: Bile acids inhibit the Notch signaling pathway with induction of CDX2 gene expression in human esophageal cells

Surgery ◽  
2009 ◽  
Vol 146 (4) ◽  
pp. 714-722 ◽  
Author(s):  
David J. Morrow ◽  
Nelly E. Avissar ◽  
Liana Toia ◽  
Eileen M. Redmond ◽  
Thomas J. Watson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Notch Signaling ◽  
Bile Acids ◽  
Signaling Pathway ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Notch Signaling Pathway

Analysis of the Relationship Between Notch Signaling Pathway and CDx2 Expression in the Development of Barrett's Esophagus

2011 ◽  
Vol 140 (5) ◽  
pp. S-307
Author(s):  
Yuji Tamagawa ◽  
Norihisa Ishimura ◽  
Goichi Uno ◽  
Takafumi Yuki ◽  
Hideaki Kazumori ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Notch Signaling Pathway ◽  
Cdx2 Expression ◽  
The Relationship

scholarly journals Notch Signaling Pathway Is Inhibited in the Development of Barrett’s Esophagus: An In Vivo and In Vitro Study

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Yun-Cang Wang ◽  
Zhi-Qiang Wang ◽  
Yong Yuan ◽  
Tao Ren ◽  
Peng-Zhi Ni ◽  
...  
Keyword(s):  
Hydrochloric Acid ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Deoxycholic Acid ◽  
Notch Signaling Pathway ◽  
Normal Esophagus ◽  
Columnar Metaplasia

Objective. To explore the role of Notch signaling in the development of Barrett’s esophagus. Methods. Patients with esophagectomy and gastric interposition were recruited as a human model of gastroesophageal reflux disease. The expressions of Notch signaling genes in normal esophagus from surgical specimen and columnar metaplasia in the esophageal remnant after esophagectomy were evaluated by real time quantitative Polymerase Chain Reaction (RT-qPCR) and immunohistochemistry (IHC). For in vitro experiments, Het-1A cells were treated with hydrochloric acid, deoxycholic acid, mixture of hydrochloric acid and deoxycholic acid, or Notch1-siRNA, and expressions of Notch1, Hes1, MUC2, and K13 were evaluated via RT-qPCR and western blot. Results. Samples were obtained from 36 patients with columnar metaplasia in the esophageal remnant. Both IHC and RT-qPCR indicated that Notch1 and Hes1 expressions were significantly higher in normal esophagus than that in metaplasia. Hydrochloric acid and deoxycholic acid suppressed Notch1, Hes1, and K13 expressions, in concert with increasing MUC2 expressions. Notch inhibition by Notch1-siRNA contributed to the downregulation of Notch1, Hes1, and K13 expressions, whereas MUC2 expression was enhanced. Conclusions. Both hydrochloric acid and deoxycholic acid could suppress Notch signaling pathway in esophageal epithelial cells, and inhibited Notch signaling has important functions in the development of Barrett’s esophagus.

scholarly journals Notch signaling pathway and Cdx2 expression in the development of Barrett's esophagus

2012 ◽  
Vol 92 (6) ◽  
pp. 896-909 ◽  
Author(s):  
Yuji Tamagawa ◽  
Norihisa Ishimura ◽  
Goichi Uno ◽  
Takafumi Yuki ◽  
Hideaki Kazumori ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Notch Signaling Pathway ◽  
Cdx2 Expression

scholarly journals Retinal Genomic Fabrics Remodeling after Optic Nerve Injury

2021 ◽  
Author(s):  
Pedro Henrique Victorino ◽  
Camila Marra ◽  
Dumitru Andrei Iacobas ◽  
Sanda Iacobas ◽  
David C Spray ◽  
...  
Keyword(s):  
Gene Expression ◽  
Optic Nerve ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Notch Signaling Pathway ◽  
Complement Cascade ◽  
Gene Expressions ◽  
Nerve Crush ◽  
Individual Gene

Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the Genomic Fabric Paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. GFP considers for the expression of each gene 3 independent characteristics: level, variability and correlation with each other gene. Thus, the 17,657 quantified genes our study generated a total of 155,911,310 values to analyze. This represents 8,830x more data per condition than a traditional transcriptomic analysis. ONC led to a 57% reduction in RGC numbers as detected by retrograde labeling with DiI. We observed a higher Relative Expression Variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Predicted Protein-Protein interaction (PPI) analysis with STRING revealed axon and neuron projection as mostly decreased processes, consistent with RGC degeneration. Conversely, immune response PPIs were found among up-regulated genes. Enrichment analysis showed that Complement Cascade and Notch Signaling Pathway, as well as Oxidative Stress and Kit Receptor Pathway were affected after ONC. To expand our studies of altered molecular pathways, we examined the pair-wise coordination of gene expressions within each pathway and within the entire transcriptome using Pearson correlations. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles mainly in Complement Cascade and Notch Signaling Pathway. This deep bioinformatic study provides novel insights beyond the regulation of individual gene expression and discloses changes in the control of expression of Complement Cascade and Notch Signaling functional pathways that may be relevant for both RGC degeneration and remodeling of the retinal tissue after ONC.

scholarly journals The Notch Pathway Intermediate HES-1 Silences CD4 Gene Expression

1998 ◽  
Vol 18 (12) ◽  
pp. 7166-7175 ◽  
Author(s):  
Han K. Kim ◽  
Gerald Siu
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Transcriptional Control ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Thymic Development ◽  
Enhancer Function ◽  
Enhancer Of Split

ABSTRACT We have previously identified a transcriptional silencer that is critical for proper expression of the CD4 gene during T-cell development. Here we report that the Hairy/Enhancer of Split homologue HES-1, a transcription factor in the lin12/Notch signaling pathway, binds to an important functional site in the CD4 silencer. Overexpression of HES-1 leads to the silencer site-dependent repression of CD4 promoter and enhancer function as well as the downregulation of endogenous CD4 expression in CD4+ CD8−TH cells. Interestingly, overexpression of an activated form of Notch1 (NotchIC) leads to the repression of CD4 promoter and enhancer function both in the presence and absence of the silencer. NotchIC-mediated CD4 silencer function is not affected by the deletion of the HES-1-binding site, indicating that multiple factors binding to CD4 transcriptional control elements are responsive to signaling from this pathway, including other silencer-binding factors. Taken together, these data are consistent with the hypothesis that the lin12/Notch signaling pathway is important in thymic development and provide a molecular mechanism via the control of CD4 gene expression in which the lin12/Notch pathway affects T-cell developmental fate.

scholarly journals Retinal Genomic Fabric Remodeling after Optic Nerve Injury

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 403
Author(s):  
Pedro Henrique Victorino ◽  
Camila Marra ◽  
Dumitru Andrei Iacobas ◽  
Sanda Iacobas ◽  
David C. Spray ◽  
...  
Keyword(s):  
Gene Expression ◽  
Optic Nerve ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Notch Signaling Pathway ◽  
Complement Cascade ◽  
Gene Expressions ◽  
Nerve Crush ◽  
Individual Gene

Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the genomic fabric paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. GFP considers three independent characteristics for the expression of each gene: level, variability, and correlation with each other gene. Thus, the 17,657 quantified genes in our study generated a total of 155,911,310 values to analyze. This represents 8830x more data per condition than a traditional transcriptomic analysis. ONC led to a 57% reduction in RGC numbers as detected by retrograde labeling with 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanine perchlorate (DiI). We observed a higher relative expression variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Predicted protein–protein interaction (PPI) analysis with STRING revealed axon and neuron projection as mostly decreased processes, consistent with RGC degeneration. Conversely, immune response PPIs were found among upregulated genes. Enrichment analysis showed that complement cascade and Notch signaling pathway, as well as oxidative stress and kit receptor pathway were affected after ONC. To expand our studies of altered molecular pathways, we examined the pairwise coordination of gene expressions within each pathway and within the entire transcriptome using Pearson correlations. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles mainly in complement cascade and Notch signaling pathway. This deep bioinformatic study provided novel insights beyond the regulation of individual gene expression and disclosed changes in the control of expression of complement cascade and Notch signaling functional pathways that may be relevant for both RGC degeneration and remodeling of the retinal tissue after ONC.

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