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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE27849 | GEO | 2011/10/02

SECONDARY ACCESSION(S): PRJNA138047

REPOSITORIES: GEO

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

Project description:This SuperSeries is composed of the following subset Series: GSE27847: Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon (part 1) GSE27848: Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon (part 2) Refer to individual Series

2011-10-01 | E-GEOD-27849 | biostudies-arrayexpress

Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon (part 2)

Project description:The risk for colon cancer is associated with nutrition, especially high fat and low calcium 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. C57BL/6 mice received a Westernized high fat and low calcium diet with or without heme (the polyporphyrin pigment of red meat). Mice received control or heme diet for 14 days. After 14 days, mice were sacrificed and colons were taken out. RNA was isolated from colon scrapings and subjected to gene expression profiling (n=7 control mice and n=9 heme-fed mice).

2011-10-01 | E-GEOD-27848 | biostudies-arrayexpress

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

Project 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. C57BL/6 mice received a Westernized diet with or without heme (the polyporphyrin pigment of red meat). Mice received control or heme diet for 14 days. After 14 days, mice were sacrificed and colons were taken out. Swiss rolls were made from the middle 2 cm of the colon. These rolls were used for LCM, and surface cells and crypts cells were separately isolated. RNA was isolated from surface and crypt cells and subjected to gene expression profiling (n=4 control mice and n=3 heme-fed mice).

2011-10-01 | E-GEOD-27847 | biostudies-arrayexpress

Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon (part 2)

2011-10-02 | GSE27848 | GEO

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

2011-10-02 | GSE27847 | GEO

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

Project description:Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon

| PRJNA138047 | ENA

Dietary heme-mediated PPAR? activation does not affect the heme-induced epithelial hyperproliferation and hyperplasia in mouse colon.

Project description: Not available

| S-EPMC3419209 | biostudies-literature

Dietary heme mediated PPARα activation does not affect the heme-induced epithelial hyperproliferation and hyperplasia in mouse colon

Project description:Red meat consumption is associated with an increased colon cancer risk. Heme, present in red meat, injures the colon surface epithelium by luminal cytotoxicity and reactive oxygen species. This surface injury is overcompensated by hyperproliferation and hyperplasia of crypt cells. Transcriptome analysis of mucosa of heme-fed mice showed, besides stress- and proliferation-related genes, many upregulated lipid metabolism-related PPARα target genes. The aim of this study was to investigate the role of PPARα in heme-induced hyperproliferation and hyperplasia. Male PPARα KO and WT mice received a purified diet with or without heme. As PPARα is proposed to protect against oxidative stress and lipid peroxidation, we hypothesized that the absence of PPARα leads to more surface injury and crypt hyperproliferation in the colon upon heme-feeding. Heme induced luminal cytotoxicity and lipid peroxidation and colonic hyperproliferation and hyperplasia to the same extent in WT and KO mice. Transcriptome analysis of colonic mucosa confirmed similar heme-induced hyperproliferation in WT and KO mice. Stainings for alkaline phosphatase activity and expression levels of Vanin-1 and Nrf2-targets indicated a compromised antioxidant defense in heme-fed KO mice. Our results suggest that the protective role of PPARα in antioxidant defense involves the Nrf2-inhibitor Fosl1, which is upregulated by heme in PPARα KO mice. We conclude that PPARα plays a protective role in colon against oxidative stress, but PPARα does not mediate heme-induced hyperproliferation. This implies that oxidative stress of surface cells is not the main determinant of heme-induced hyperproliferation and hyperplasia.

2012-08-22 | GSE37006 | GEO

Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon.

Project description: Not available

| S-EPMC4538683 | biostudies-literature

MiR-200c/FUT4 axis prevents the proliferation of colon cancer cells by downregulating the Wnt/?-catenin pathway.

Project description: Not available

| S-EPMC7784291 | biostudies-literature