Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation

Mehmet Coskun, Christoffer Soendergaard, Steffen Jørgensen, Katja Dahlgaard, Lene Buhl Riis, Ole Haagen Nielsen, Albin Gustav Sandelin, Jesper Troelsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

The expression of Caudal-related homeobox transcription factor 2 (CDX2) is impaired by tumor necrosis factor-α (TNF-α)-mediated activation of nuclear factor-κB (NF-κB) in ulcerative colitis (UC). Laminin subunit γ2 (LAMC2) is an epithelial basement membrane protein implicated in cell migration, proliferation, differentiation, as well as tumor invasion and intestinal inflammation, and its expression is enhanced by TNF-α in a NF-κB-dependent regulation of the recently identified LAMC2 enhancer. The aim was to determine whether CDX2 is involved in the basal regulation of LAMC2 in epithelial cells and to assess the influence of inflammation. Transcriptional regulation of LAMC2 was examined by reporter gene assays, overexpression, and shRNA-mediated knock-down of CDX2. CDX2-DNA interactions were assessed by chromatin immunoprecipitation on Caco-2 cells without or with TNF-α, as well as in purified colonic human epithelial cells. Immunohistochemical staining and quantitative reverse-transcription polymerase chain reaction analyses were used to measure the expression of CDX2 and LAMC2 in colonic biopsies from healthy controls and patients with UC. These data indicate that CDX2 directly regulates LAMC2 gene expression through interaction with elements in the LAMC2 promoter region. We further revealed an inverse effect of inflammation on CDX2 and LAMC2. The data presented provide a novel insight into how CDX2 is implicated in the transcriptional regulation of LAMC2 in intestinal epithelial cells, a function that is impaired during mucosal inflammation where a high level of TNF-α is present.
OriginalsprogEngelsk
TidsskriftJournal of Cellular Biochemistry
Vol/bind118
Udgave nummer2
Sider (fra-til)298-307
ISSN0730-2312
DOI
StatusUdgivet - feb. 2017

Citer dette

Coskun, Mehmet ; Soendergaard, Christoffer ; Jørgensen, Steffen ; Dahlgaard, Katja ; Riis, Lene Buhl ; Nielsen, Ole Haagen ; Sandelin, Albin Gustav ; Troelsen, Jesper. / Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation. I: Journal of Cellular Biochemistry. 2017 ; Bind 118, Nr. 2. s. 298-307.
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title = "Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation",
abstract = "The expression of Caudal-related homeobox transcription factor 2 (CDX2) is impaired by tumor necrosis factor-α (TNF-α)-mediated activation of nuclear factor-κB (NF-κB) in ulcerative colitis (UC). Laminin subunit γ2 (LAMC2) is an epithelial basement membrane protein implicated in cell migration, proliferation, differentiation, as well as tumor invasion and intestinal inflammation, and its expression is enhanced by TNF-α in a NF-κB-dependent regulation of the recently identified LAMC2 enhancer. The aim was to determine whether CDX2 is involved in the basal regulation of LAMC2 in epithelial cells and to assess the influence of inflammation. Transcriptional regulation of LAMC2 was examined by reporter gene assays, overexpression, and shRNA-mediated knock-down of CDX2. CDX2-DNA interactions were assessed by chromatin immunoprecipitation on Caco-2 cells without or with TNF-α, as well as in purified colonic human epithelial cells. Immunohistochemical staining and quantitative reverse-transcription polymerase chain reaction analyses were used to measure the expression of CDX2 and LAMC2 in colonic biopsies from healthy controls and patients with UC. These data indicate that CDX2 directly regulates LAMC2 gene expression through interaction with elements in the LAMC2 promoter region. We further revealed an inverse effect of inflammation on CDX2 and LAMC2. The data presented provide a novel insight into how CDX2 is implicated in the transcriptional regulation of LAMC2 in intestinal epithelial cells, a function that is impaired during mucosal inflammation where a high level of TNF-α is present.",
author = "Mehmet Coskun and Christoffer Soendergaard and Steffen J{\o}rgensen and Katja Dahlgaard and Riis, {Lene Buhl} and Nielsen, {Ole Haagen} and Sandelin, {Albin Gustav} and Jesper Troelsen",
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Coskun, M, Soendergaard, C, Jørgensen, S, Dahlgaard, K, Riis, LB, Nielsen, OH, Sandelin, AG & Troelsen, J 2017, 'Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation', Journal of Cellular Biochemistry, bind 118, nr. 2, s. 298-307. https://doi.org/10.1002/jcb.25636

Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation. / Coskun, Mehmet; Soendergaard, Christoffer; Jørgensen, Steffen; Dahlgaard, Katja; Riis, Lene Buhl; Nielsen, Ole Haagen; Sandelin, Albin Gustav; Troelsen, Jesper.

I: Journal of Cellular Biochemistry, Bind 118, Nr. 2, 02.2017, s. 298-307.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation

AU - Coskun, Mehmet

AU - Soendergaard, Christoffer

AU - Jørgensen, Steffen

AU - Dahlgaard, Katja

AU - Riis, Lene Buhl

AU - Nielsen, Ole Haagen

AU - Sandelin, Albin Gustav

AU - Troelsen, Jesper

N1 - Publisher addition to reuse the accepted version of this article: "This is the peer reviewed version of the following article: Coskun, M., Soendergaard, C., Jørgensen, S., Dahlgaard, K., Riis, L. B., Nielsen, O. H., ... Troelsen, J. (2017). Regulation of Laminin 2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation. Journal of Cellular Biochemistry, 298-307, which has been published in final form at DOI: 10.1002/jcb.25636]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."

PY - 2017/2

Y1 - 2017/2

N2 - The expression of Caudal-related homeobox transcription factor 2 (CDX2) is impaired by tumor necrosis factor-α (TNF-α)-mediated activation of nuclear factor-κB (NF-κB) in ulcerative colitis (UC). Laminin subunit γ2 (LAMC2) is an epithelial basement membrane protein implicated in cell migration, proliferation, differentiation, as well as tumor invasion and intestinal inflammation, and its expression is enhanced by TNF-α in a NF-κB-dependent regulation of the recently identified LAMC2 enhancer. The aim was to determine whether CDX2 is involved in the basal regulation of LAMC2 in epithelial cells and to assess the influence of inflammation. Transcriptional regulation of LAMC2 was examined by reporter gene assays, overexpression, and shRNA-mediated knock-down of CDX2. CDX2-DNA interactions were assessed by chromatin immunoprecipitation on Caco-2 cells without or with TNF-α, as well as in purified colonic human epithelial cells. Immunohistochemical staining and quantitative reverse-transcription polymerase chain reaction analyses were used to measure the expression of CDX2 and LAMC2 in colonic biopsies from healthy controls and patients with UC. These data indicate that CDX2 directly regulates LAMC2 gene expression through interaction with elements in the LAMC2 promoter region. We further revealed an inverse effect of inflammation on CDX2 and LAMC2. The data presented provide a novel insight into how CDX2 is implicated in the transcriptional regulation of LAMC2 in intestinal epithelial cells, a function that is impaired during mucosal inflammation where a high level of TNF-α is present.

AB - The expression of Caudal-related homeobox transcription factor 2 (CDX2) is impaired by tumor necrosis factor-α (TNF-α)-mediated activation of nuclear factor-κB (NF-κB) in ulcerative colitis (UC). Laminin subunit γ2 (LAMC2) is an epithelial basement membrane protein implicated in cell migration, proliferation, differentiation, as well as tumor invasion and intestinal inflammation, and its expression is enhanced by TNF-α in a NF-κB-dependent regulation of the recently identified LAMC2 enhancer. The aim was to determine whether CDX2 is involved in the basal regulation of LAMC2 in epithelial cells and to assess the influence of inflammation. Transcriptional regulation of LAMC2 was examined by reporter gene assays, overexpression, and shRNA-mediated knock-down of CDX2. CDX2-DNA interactions were assessed by chromatin immunoprecipitation on Caco-2 cells without or with TNF-α, as well as in purified colonic human epithelial cells. Immunohistochemical staining and quantitative reverse-transcription polymerase chain reaction analyses were used to measure the expression of CDX2 and LAMC2 in colonic biopsies from healthy controls and patients with UC. These data indicate that CDX2 directly regulates LAMC2 gene expression through interaction with elements in the LAMC2 promoter region. We further revealed an inverse effect of inflammation on CDX2 and LAMC2. The data presented provide a novel insight into how CDX2 is implicated in the transcriptional regulation of LAMC2 in intestinal epithelial cells, a function that is impaired during mucosal inflammation where a high level of TNF-α is present.

U2 - 10.1002/jcb.25636

DO - 10.1002/jcb.25636

M3 - Journal article

VL - 118

SP - 298

EP - 307

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 2

ER -