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

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IJssennagger, Noortje, Rijnierse, Anneke, de Wit, Nicole, Jonker-Termont, Denise, Dekker, Jan, Müller, Michael ORCID: https://orcid.org/0000-0002-5930-9905 and van der Meer, Roelof (2012) Dietary haem stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon. Gut, 61 (7). pp. 1041-1049. ISSN 0017-5749

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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)

Item Type: Article
Uncontrolled 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,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
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Depositing User: Pure Connector
Date Deposited: 18 Dec 2013 12:16
Last Modified: 12 Jun 2024 14:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/47056
DOI: 10.1136/gutjnl-2011-300239

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