Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon (part 1)

  • Noortje IJssennagger (Creator)
  • A. Rijnierse (Creator)
  • Michael Muller (Creator)
  • Roelof van der Meer (Creator)

Dataset

Description

The risk for colon cancer is associated with nutrition, especially with diets high in red meat. Red meat contains the iron porphyrin pigment heme, which induces cytotoxicity of the colon contents and epithelial hyperproliferation. Using a mouse model, we showed that heme caused damage to the colonic surface epithelium and induced compensatory hyperproliferation. Expression levels of heme- and stress-related genes show that heme affects surface cells and not directly crypt cells. Therefore, injured surface cells should signal to crypt TA cells to induce compensatory hyperproliferation. Surface-specific downregulated inhibitors of proliferation were Wnt inhibitory factor 1, Indian Hedgehog, Bone morphogenic protein 2 and possibly Interleukin-15. Heme also upregulated Amphiregulin, Epiregulin and Cyclooxygenase-2 mRNA in the surface cells, however, their protein/metabolite levels were not increased as heme induced surface-specific translation repression by increasing 4E-BP1. Therefore, we conclude that heme induced colonic hyperproliferation and hyperplasia by repressing feedback inhibition of proliferation.
Date made available2 Oct 2011
PublisherWageningen University

Research Output

Dietary haem stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon

IJssennagger, N., Rijnierse, A., de Wit, N., Jonker-Termont, D. S. M. L., Dekker, J., Muller, M. R. & van der Meer, R., 2012, In : Gut. 61, 7, p. 1041-1049

Research output: Contribution to journalArticleAcademicpeer-review

  • 38 Citations (Scopus)

    Dietary heme alters microbiota and mucosa of mouse colon without functional changes in host-microbe cross-talk

    IJssenagger, N., Derrien, M., van Doorn, G. M., Rijnierse, A., van den Bogert, B., Muller, M. R., Dekker, J., Kleerebezem, M. & van der Meer, R., 2012, In : PLoS ONE. 7, 12, 10 p., e49868.

    Research output: Contribution to journalArticleAcademicpeer-review

    Open Access
  • 55 Citations (Scopus)

    Cite this

    IJssennagger, N. (Creator), Rijnierse, A. (Creator), Muller, M. (Creator), van der Meer, R. (Creator) (2 Oct 2011). Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon (part 1). Wageningen University.