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Wnt signaling is boosted during intestinal regeneration by a CD44-positive feedback loop

descriptionPublicationkeyboard_double_arrow_right Article , Conference object , Other literature type 21 Feb 2022 Germany English Publisher:Springer Science and Business Media LLCJournal:Cell Death & Disease, volume 13 (eissn: 2041-4889, Copyright policy )Funded by:UKRI | DTG Competition 2011/5
Authors: Romina J. Walter; Steffen J. Sonnentag; Leonel Munoz-Sagredo; Melanie Merkel; Ludovic Richert; Felix Bunert; Yvonne M. Heneka; +8 Authors

doi: 10.1038/s41419-022-04607-0 , 10.5445/ir/1000143598

pmid: 35190527

pmc: PMC8861016

Wnt signaling is boosted during intestinal regeneration by a CD44-positive feedback loop

Abstract

AbstractEnhancement of Wnt signaling is fundamental for stem cell function during intestinal regeneration. Molecular modules control Wnt activity by regulating signal transduction. CD44 is such a positive regulator and a Wnt target gene. While highly expressed in intestinal crypts and used as a stem cell marker, its role during intestinal homeostasis and regeneration remains unknown. Here we propose a CD44 positive-feedback loop that boosts Wnt signal transduction, thus impacting intestinal regeneration. Excision of Cd44 in Cd44fl/fl;VillinCreERT2 mice reduced Wnt target gene expression in intestinal crypts and affected stem cell functionality in organoids. Although the integrity of the intestinal epithelium was conserved in mice lacking CD44, they were hypersensitive to dextran sulfate sodium, and showed more severe inflammation and delayed regeneration. We localized the molecular function of CD44 at the Wnt signalosome, and identified novel DVL/CD44 and AXIN/CD44 complexes. CD44 thus promotes optimal Wnt signaling during intestinal regeneration.

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Keywords

Life sciences; biology, info:eu-repo/classification/ddc/570, 570, QH573-671, biology, Stem Cells, 610, Life sciences, Article, Feedback, Intestines, Mice, Animals, ddc:570, Intestinal Mucosa, Cytology, Wnt Signaling Pathway, Cell Proliferation

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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    		 22
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    		 Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    		 Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    		 Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
22
Top 10%
Average
Top 10%
Green
gold
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