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

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Abstract

Background

Wnt-β-catenin signaling is essential for homeostasis of intestinal stem cells in mice and is thought to promote intestinal crypt fission.

Aims

The aim of this study was to investigate Wnt-β-catenin signaling in intestinal crypts of human infants.

Methods

Duodenal biopsies from nine infants (mean, range 0.9 years, 0.3–2 years) and 11 adults (mean, range 43 years, 34–71 years) were collected endoscopically. Active β-catenin signaling was assessed by cytoplasmic and nuclear β-catenin, nuclear c-Myc, and cytoplasmic Axin-2 expression in the base of crypts. Tissues were stained by an immunoperoxidase staining technique and quantified as pixel energy using cumulative signal analysis. Data were expressed as mean ± SD and significance assessed by Student’s t test.

Results

Crypt fission was significantly higher in infants compared to adults (16 ± 8.6% versus 0.7 ± 0.6%, respectively, p < 0.0001). Expression of cytoplasmic and nuclear β-catenin was 1.8-fold (p < 0.0001) and 2.9-fold (p < 0.0001) higher in infants, respectively, while cytoplasmic Axin-2 was 3.1-fold (p < 0.0001) increased in infants. c-Myc expression was not significantly different between infants and adults. Expression was absent in Paneth cells but present in the transit amplifying zone of crypts. Crypt base columnar cells, which were intercalated between Paneth cells, expressed c-Myc.

Conclusions

Wnt-β-catenin signaling was active in crypt base columnar cells (i.e., intestinal stem cells) in human infants. This signaling could promote crypt fission during infancy. Wnt-β-catenin signaling likely acts in concert with other pathways to promote postnatal growth.

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Funding

Zenab Dudhwala gratefully received a Faculty of Health Science Divisional Scholarship from the University of Adelaide. The authors are grateful for funding from the Private Practice Fund of the Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia.

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Authors and Affiliations

  1. Gastroenterology Research Laboratory, Discipline of Medicine, University of Adelaide, and Basil Hetzel Institute for Translational Health Research, 37a Woodville Road, Woodville South, SA, 5011, Australia

    Zenab M. Dudhwala & Adrian G. Cummins

  2. Solid Cancer Regulation Group, Discipline of Surgery, University of Adelaide, and the Basil Hetzel Institute for Translational Health Research, 37a Woodville Road, Woodville South, SA, 5011, Australia

    Paul A. Drew

  3. College of Nursing and Health Sciences, Flinders University, Adelaide, SA, 5001, Australia

    Paul A. Drew

  4. Department of Gastroenterology, Women’s and Children’s Hospital, 72 King William Road, North Adelaide, SA, 5006, Australia

    Gordon S. Howarth & David Moore

  5. School of Animal and Veterinary Sciences, Roseworthy Campus, University of Adelaide, Roseworthy, SA, 5371, Australia

    Gordon S. Howarth

  6. Discipline of Paediatrics, University of Adelaide, 72 King William Road, North Adelaide, SA, 5006, Australia

    David Moore

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  1. Zenab M. Dudhwala
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  2. Paul A. Drew
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Correspondence to Zenab M. Dudhwala.

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Dudhwala, Z.M., Drew, P.A., Howarth, G.S. et al. Active β-Catenin Signaling in the Small Intestine of Humans During Infancy. Dig Dis Sci 64, 76–83 (2019). https://doi.org/10.1007/s10620-018-5286-y

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  • DOI: https://doi.org/10.1007/s10620-018-5286-y

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