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

Noortje IJssennagger, Anneke Rijnierse, Nicole de Wit, Denise Jonker-Termont, Jan Dekker, Michael Müller, Roelof Van Der Meer

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Objective: Colon cancer is a leading cause of cancer deaths in Western countries and is associated with diets high in red meat. Haem, the iron-porphyrin pigment of red meat, induces cytotoxicity of gut contents and damages the colon surface epithelium. Compensatory hyperproliferation leads to epithelial hyperplasia which increases the risk of colon cancer. The aim of this study was to identify molecules signalling from the surface epithelium to the crypt to initiate hyperproliferation upon stress induced by haem. Methods: C57Bl6/J mice (n=9/group) received a 'westernised' control diet (40 en% fat) with or without 0.5 mmol/g haem for 14 days. Colon mucosa was used to quantify cell proliferation and for microarray transcriptome analysis. Gene expression profiles of surface and crypt cells were compared using laser capture microdissection. Protein levels of potential signalling molecules were quantified. Results: Haem-fed mice showed epithelial hyperproliferation and decreased apoptosis, resulting in hyperplasia. Microarray analysis of the colon mucosa showed 3710 differentially expressed genes (false discovery rate (q)
Original languageEnglish
Pages (from-to)1041-1049
Number of pages9
JournalGut
Volume61
Issue number7
DOIs
Publication statusPublished - 1 Jul 2012

Keywords

  • Animals
  • Cell Proliferation
  • Colon
  • Colonic Neoplasms
  • Dietary Supplements
  • Down-Regulation
  • Epithelial Cells
  • Feedback, Physiological
  • Gene Expression
  • Gene Expression Profiling
  • Heme
  • Intestinal Mucosa
  • Laser Capture Microdissection
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oligonucleotide Array Sequence Analysis
  • Signal Transduction
  • Transcriptome

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