Active β-Catenin Signaling in the Small Intestine of Humans During Infancy

Dudhwala, Zenab M.; Drew, Paul A.; Howarth, Gordon S.; Moore, David; Cummins, Adrian G.

doi:10.1007/s10620-018-5286-y

Cited by 6 publications

(11 citation statements)

References 41 publications

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“…Later Langlands et al 28 Crypt fission was dependent on LGR5+ cells in the rat, as Dickkopf treatment reduced both LGR5+ cells and crypt fission. The present work extends the previous studies, [34][35][36] which showed elevated Wnt signalling at the base of crypts in rats and humans. Those studies did not examine LGR5+ cells.…”

Section: Discussionsupporting

confidence: 91%

“…We cannot explain this discrepancy other than to comment that inhibition with Dickkopf is very selective but less severe than with PORCN inhibitors. The human has similar features of high Wnt-β-catenin signalling during infancy, 36 a peak of crypt fission during infancy, 8 and an expanded population of LGR5+ stem cells (figure 3). Dickkopf treatment did not affect the mitotic count per crypt, which must be determined by the higher proliferation of the progeny of LGR5+ cells in the transit amplifying zone.…”

Section: Discussionmentioning

confidence: 98%

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Intestinal stem cells promote crypt fission during postnatal growth of the small intestine

Dudhwala

Hammond

Howarth

et al. 2020

BMJ Open Gastroenterol

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ObjectiveWnt-β-catenin signalling is essential for intestinal stem cells. Our aim was to investigate the relationship between intestinal stem cells and crypt fission which peaks during infancy.DesignDuodenal biopsies were obtained during endoscopy to assess the severity of reflux oesophagitis of 15 infants, children and teenagers, which would not affect the duodenum. Samples of small intestine were also obtained from rats 7–72 days of life. Crypt fission was assessed using microdissection of 100 whole crypts and recording the percentage of bifid crypts. Intestinal LGR5+ stem cells were identified by in situ hybridisation. Rats were treated with Dickkopf to block Wnt-β-catenin signalling.ResultsCrypt fission peaked during infancy before declining after 3–4 years in humans and after 21 days of life in rats. Occasional mitotic figures were seen in bifid crypts during early fission. Stem cells were elevated for a greater period during infancy and childhood in humans. Clustering of Paneth cells was present around the stem cells at the crypt base. Dickkopf reduced the number of stem cells and crypt fission to 45% and 29%, respectively, of control values, showing dependence of both crypt fission and Lgr5+ stem cells on Wnt signalling. However, Dickkopf did not decrease mitotic count per crypt, indicating a difference in signalling between stem cells and their progeny in the transit amplifying zone.ConclusionCrypt fission peaks during infancy and is dependent on intestinal stem cells. This is relatively hidden by ‘a cloak of invisibility’ due to the low proliferation of stem cells.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 98%

Intestinal stem cells promote crypt fission during postnatal growth of the small intestine

Dudhwala

Hammond

Howarth

et al. 2020

BMJ Open Gastroenterol

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“…Therefore, β‐catenin is no longer degraded (non‐phospho β‐catenin) but functions as a transcriptional factor. The target genes of β‐catenin, such as c‐MYC and cyclin D1, will be up‐regulated to stimulate the proliferation of intestinal epithelia 21‐23 . It is not clear whether β‐catenin signalling pathway is related to COX‐2 expression during inflammatory stimulation of liver fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of cyclooxygenase‐2 enhanced intestinal epithelial homeostasis via suppressing β‐catenin signalling pathway in experimental liver fibrosis

Zhang

Tai

Zhao

et al. 2021

J Cellular Molecular Medi

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The intestinal barrier dysfunction is crucial for the development of liver fibrosis but can be disturbed by intestinal chronic inflammation characterized with cyclooxygenase‐2 (COX‐2) expression. This study focused on the unknown mechanism by which COX‐2 regulates intestinal epithelial homeostasis in liver fibrosis. The animal models of liver fibrosis induced with TAA were established in rats and in intestinal epithelial–specific COX‐2 knockout mice. The impacts of COX‐2 on intestinal epithelial homeostasis via suppressing β‐catenin signalling pathway were verified pharmacologically and genetically in vivo. A similar assumption was tested in Ls174T cells with goblet cell phenotype in vitro. Firstly, disruption of intestinal epithelial homeostasis in cirrhotic rats was ameliorated by celecoxib, a selective COX‐2 inhibitor. Then, β‐catenin signalling pathway in cirrhotic rats was associated with the activation of COX‐2. Furthermore, intestinal epithelial–specific COX‐2 knockout could suppress β‐catenin signalling pathway and restore the disruption of ileal epithelial homeostasis in cirrhotic mice. Moreover, the effect of COX‐2/PGE2 was dependent on the β‐catenin signalling pathway in Ls174T cells. Therefore, inhibition of COX‐2 may enhance intestinal epithelial homeostasis via suppression of the β‐catenin signalling pathway in liver fibrosis.

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Section: Introductionmentioning

confidence: 99%

“…The Wnt-β-catenin pathway is active in the small intestine during infancy of both rats [1] and humans [2]. This activity promotes positioning of Paneth cells at the base of crypts to form a stem cell niche [3], and protects intestinal stem cells from apoptosis such that intestinal growth may proceed during infancy [2]. Enhanced Wnt-β-catenin signaling in the small intestine is present during infancy in both rats and humans, as shown by peaks of cytoplasmic and nuclear β-catenin, and of cytoplasmic axin-2 [1,2].…”

Section: Introductionmentioning

confidence: 99%

Wnt2b, Wnt3, and R-Spondin-1 Promote β-Catenin Signaling in the Small Intestine during Infancy

M¹,

P²,

J³

et al. 2021

Insights Stem Cell Res Ther

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Active β-Catenin Signaling in the Small Intestine of Humans During Infancy

Cited by 6 publications

References 41 publications

Intestinal stem cells promote crypt fission during postnatal growth of the small intestine

Intestinal stem cells promote crypt fission during postnatal growth of the small intestine

Inhibition of cyclooxygenase‐2 enhanced intestinal epithelial homeostasis via suppressing β‐catenin signalling pathway in experimental liver fibrosis

Wnt2b, Wnt3, and R-Spondin-1 Promote β-Catenin Signaling in the Small Intestine during Infancy

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