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Kaiso differentially regulates components of the Notch signaling pathway in intestinal cells

Overview of attention for article published in Cell Communication and Signaling, June 2017
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  • Above-average Attention Score compared to outputs of the same age (61st percentile)

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Title
Kaiso differentially regulates components of the Notch signaling pathway in intestinal cells
Published in
Cell Communication and Signaling, June 2017
DOI 10.1186/s12964-017-0178-x
Pubmed ID
Authors

Shaiya C. Robinson, Kristina Klobucar, Christina C. Pierre, Amna Ansari, Svetlana Zhenilo, Egor Prokhortchouk, Juliet M. Daniel

Abstract

In mammalian intestines, Notch signaling plays a critical role in mediating cell fate decisions; it promotes the absorptive (or enterocyte) cell fate, while concomitantly inhibiting the secretory cell fate (i.e. goblet, Paneth and enteroendocrine cells). We recently reported that intestinal-specific Kaiso overexpressing mice (Kaiso (Tg) ) exhibited chronic intestinal inflammation and had increased numbers of all three secretory cell types, hinting that Kaiso might regulate Notch signaling in the gut. However, Kaiso's precise role in Notch signaling and whether the Kaiso (Tg) secretory cell fate phenotype was linked to Kaiso-induced inflammation had yet to be elucidated. Intestines from 3-month old Non-transgenic and Kaiso (Tg) mice were "Swiss" rolled and analysed for the expression of Notch1, Dll-1, Jagged-1, and secretory cell markers by immunohistochemistry and immunofluorescence. To evaluate inflammation, morphological analyses and myeloperoxidase assays were performed on intestines from 3-month old Kaiso (Tg) and control mice. Notch1, Dll-1 and Jagged-1 expression were also assessed in stable Kaiso-depleted colon cancer cells and isolated intestinal epithelial cells using real time PCR and western blotting. To assess Kaiso binding to the DLL1, JAG1 and NOTCH1 promoter regions, chromatin immunoprecipitation was performed on three colon cancer cell lines. Here we demonstrate that Kaiso promotes secretory cell hyperplasia independently of Kaiso-induced inflammation. Moreover, Kaiso regulates several components of the Notch signaling pathway in intestinal cells, namely, Dll-1, Jagged-1 and Notch1. Notably, we found that in Kaiso (Tg) mice intestines, Notch1 and Dll-1 expression are significantly reduced while Jagged-1 expression is increased. Chromatin immunoprecipitation experiments revealed that Kaiso associates with the DLL1 and JAG1 promoter regions in a methylation-dependent manner in colon carcinoma cell lines, suggesting that these Notch ligands are putative Kaiso target genes. Here, we provide evidence that Kaiso's effects on intestinal secretory cell fates precede the development of intestinal inflammation in Kaiso (Tg) mice. We also demonstrate that Kaiso inhibits the expression of Dll-1, which likely contributes to the secretory cell phenotype observed in our transgenic mice. In contrast, Kaiso promotes Jagged-1 expression, which may have implications in Notch-mediated colon cancer progression.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 21%
Student > Bachelor 5 17%
Researcher 3 10%
Student > Doctoral Student 2 7%
Student > Master 2 7%
Other 3 10%
Unknown 8 28%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 21%
Agricultural and Biological Sciences 4 14%
Medicine and Dentistry 4 14%
Immunology and Microbiology 2 7%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Other 2 7%
Unknown 10 34%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 July 2017.
All research outputs
#7,474,629
of 22,981,247 outputs
Outputs from Cell Communication and Signaling
#208
of 1,008 outputs
Outputs of similar age
#119,643
of 316,843 outputs
Outputs of similar age from Cell Communication and Signaling
#3
of 4 outputs
Altmetric has tracked 22,981,247 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 1,008 research outputs from this source. They receive a mean Attention Score of 4.0. This one has done well, scoring higher than 78% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 316,843 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 61% of its contemporaries.
We're also able to compare this research output to 4 others from the same source and published within six weeks on either side of this one.