Retinoid X Receptor α and Retinoic Acid Receptor γ Mediate Expression of Genes Encoding Tight-Junction Proteins and Barrier Function in F9 Cells during Visceral Endodermal Differentiation

Kubota, Hiromi; Chiba, Hideki; Takakuwa, Yasunari; Osanai, Makoto; Tobioka, Hirotoshi; Kohama, Gen–iku; Mori, Makoto; Sawada, Norimasa

doi:10.1006/excr.2000.5113

Cited by 90 publications

(89 citation statements)

References 46 publications

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“…Another hypothesis is that cingulin mutation affects the level of mRNAs coding for TJ proteins indirectly, by perturbing transcriptional and/or translational regulatory networks that control the expression and mRNA stability of TJ-protein genes. Consistent with this possibility, we noticed that the genes whose mRNA levels were increased in cingulin-mutant EBs (claudin-2, claudin-6, claudin-7 and occludin) are the same as those that are induced by retinoic-acid treatment or overexpression of the hepatocyte nuclear receptor HNF-4α in F9 murine embryonal carcinoma cells (Chiba et al, 2003;Kubota et al, 2001). Strikingly, we showed increased transcript levels for the transcription factors HNF-4α, GATA-4 and GATA-6 in homozygous (-/-) EBs.…”

Section: Discussionsupporting

confidence: 67%

Disruption of the cingulin gene does not prevent tight junction formation but alters gene expression

Guillemot

Hammar

Kaister

et al. 2004

Journal of Cell Science

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Cingulin, a component of vertebrate tight junctions, contains a head domain that controls its junctional recruitment and protein interactions. To determine whether lack of junctional cingulin affects tight-junction organization and function, we examined the phenotype of embryoid bodies derived from embryonic stem cells carrying one or two alleles of cingulin with a targeted deletion of the exon coding for most of the predicted head domain. In homozygous (–/–) embryoid bodies, no full-length cingulin was detected by immunoblotting and no junctional labeling was detected by immunofluorescence. In hetero- and homozygous (+/– and –/–) embryoid bodies, immunoblotting revealed a Triton-soluble, truncated form of cingulin, increased levels of the tight junction proteins ZO-2, occludin, claudin-6 and Lfc, and decreased levels of ZO-1. The +/– and –/– embryoid bodies contained epithelial cells with normal tight junctions, as determined by freeze-fracture and transmission electron microscopy, and a biotin permeability assay. The localization of ZO-1, occludin and claudin-6 appeared normal in mutant epithelial cells, indicating that cingulin is not required for their junctional recruitment. Real-time quantitative reverse-transcription PCR (real-time qRT-PCR) showed that differentiation of embryonic stem cells into embryoid bodies was associated with up-regulation of mRNAs for several tight junction proteins. Microarray analysis and real-time qRT-PCR showed that cingulin mutation caused a further increase in the transcript levels of occludin, claudin-2, claudin-6 and claudin-7, which were probably due to an increase in expression of GATA-6, GATA-4 and HNF-4α, transcription factors implicated in endodermal differentiation. Thus, lack of junctional cingulin does not prevent tight-junction formation, but gene expression and tight junction protein levels are altered by the cingulin mutation.

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Section: Discussionsupporting

confidence: 67%

Disruption of the cingulin gene does not prevent tight junction formation but alters gene expression

Guillemot

Hammar

Kaister

et al. 2004

Journal of Cell Science

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“…Of interest, the outer layer of the embryoid bodies forms a tight junction, whereas the monolayer culture of ES cells express a very low level of claudins (Kubota et al, 2001) (data not shown). Polar distribution of E-cadherin might lead to signals such as activation of Cdc42/Rac and atypical protein kinases C as well as membrane sequestration of β-catenin (Etienne- Manneville and Hall, 2002).…”

Section: Discussionmentioning

confidence: 95%

Aggregation of embryonic stem cells induces Nanog repression and primitive endoderm differentiation

Hamazaki

Oka

Yamanaka

et al. 2004

Journal of Cell Science

101

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When embryonic stem cells are allowed to aggregate, the outer layer of the aggregated spheres (referred to as embryoid bodies) differentiates into primitive endoderm. This initial specification of cell lineage facilitates further differentiation of the inner mass of the embryoid bodies. These processes are considered to recapitulate early embryonic development from the blastocyst stage to the egg-cylinder stage. Formation of the primitive endoderm layer in the embryoid bodies was induced solely by aggregation of embryonic stem cells, in the presence of leukemia inhibitory factor/STAT3 and serum/BMP4, which were considered to be sufficient for embryonic stem cell self-renewal. Interestingly, cell aggregation by itself induced Nanog repression at the outer layer, which was essential for aggregation-induced primitive endoderm formation. These data illustrate aggregation-based cell-fate specification during early embryonic development, when downregulation of Nanog plays a crucial role.

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“…Remarkably, in addition to the inhibitory effect of RA on TLR responsiveness in DCs, RA has been shown to increase intestinal epithelial barrier function (60,61). Therefore, in the case of vitamin A deficiency, the intestinal barrier might be compromised, resulting in enhanced invasion of bacteria and enhanced exposure of DCs to TLR ligands.…”

Section: Discussionmentioning

confidence: 99%

Expression of Retinaldehyde Dehydrogenase Enzymes in Mucosal Dendritic Cells and Gut-Draining Lymph Node Stromal Cells Is Controlled by Dietary Vitamin A

Molenaar¹,

Knippenberg²,

Goverse³

et al. 2011

The Journal of Immunology

154

150

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The vitamin A metabolite retinoic acid (RA) plays a crucial role in mucosal immune responses. We demonstrate in this study that RA-producing retinaldehyde dehydrogenase (RALDH) enzymes are postnatally induced in mesenteric lymph node (MLN) dendritic cells (DCs) and MLN stromal cells. RALDH enzyme activity in lamina propria-derived CD103+ MLN-DCs did not depend on TLR signaling. Remarkably, RA itself could directly induce RALDH2 in both DCs and stromal cells in vitro. Furthermore, upon provision of a vitamin A-deficient diet, it was found that RA-mediated signaling was strongly reduced within the small intestines, while RALDH2 mRNA and RALDH enzyme activity in lamina propria DCs and MLN-DCs, as well as RALDH2 mRNA expression in MLN stromal cells, were strongly diminished. Moreover, supply of vitamin A to vitamin A-deficient mice restored RA-mediated signaling in the intestine and RALDH activity in lamina propria-derived CD103+ MLN-DCs. Our results show that RA-dependent signaling within the intestine is indispensable for RALDH activity in the draining MLN.

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Retinoid X Receptor α and Retinoic Acid Receptor γ Mediate Expression of Genes Encoding Tight-Junction Proteins and Barrier Function in F9 Cells during Visceral Endodermal Differentiation

Cited by 90 publications

References 46 publications

Disruption of the cingulin gene does not prevent tight junction formation but alters gene expression

Disruption of the cingulin gene does not prevent tight junction formation but alters gene expression

Aggregation of embryonic stem cells induces Nanog repression and primitive endoderm differentiation

Expression of Retinaldehyde Dehydrogenase Enzymes in Mucosal Dendritic Cells and Gut-Draining Lymph Node Stromal Cells Is Controlled by Dietary Vitamin A

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