Evidence map›Paper›PMID 24788806›Full record

ArticlePloS one2014

Retinoic acid and GM-CSF coordinately induce retinal dehydrogenase 2 (RALDH2) expression through cooperation between the RAR/RXR complex and Sp1 in dendritic cells.

Yoshiharu Ohoka, Aya Yokota-Nakatsuma, Naoko Maeda, Hajime Takeuchi, Makoto Iwata

Abstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. A novelDiscovery immunology · 2023
    Article
  8. Retinoid metabolism: new insights.Journal of molecular endocrinology · 2022
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Identification of compounds that modulate retinol signaling using a cell-based qHTS assay.Toxicology in vitro : an international journal published in association with BIBRA · 2016
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Yoshiharu OhokaLaboratory of Immunology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki-shi, Kagawa, Japan; Japan Science and Technology Agency, CREST, Chiyoda-ku, Tokyo, Japan.
Aya Yokota-NakatsumaLaboratory of Immunology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki-shi, Kagawa, Japan; Japan Science and Technology Agency, CREST, Chiyoda-ku, Tokyo, Japan.
Naoko MaedaLaboratory of Immunology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki-shi, Kagawa, Japan; Japan Science and Technology Agency, CREST, Chiyoda-ku, Tokyo, Japan.
Hajime TakeuchiLaboratory of Immunology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki-shi, Kagawa, Japan; Japan Science and Technology Agency, CREST, Chiyoda-ku, Tokyo, Japan.
Makoto IwataLaboratory of Immunology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki-shi, Kagawa, Japan; Japan Science and Technology Agency, CREST, Chiyoda-ku, Tokyo, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Retinoic acid (RA)-producing dendritic cells (DCs) play critical roles in gut immunity. Retinal dehydrogenase 2 (RALDH2) encoded by Aldh1a2 is a key enzyme for generating RA in DCs. Granulocyte-macrophage colony-stimulating factor (GM-CSF) potently induces RALDH2 expression in DCs in an RA-dependent manner, and RA alone weakly induces the expression. However, how GM-CSF and RA induce RALDH2 expression remains unclear. Here, we show that GM-CSF-induced activation of the transcription factor Sp1 and RA-dependent signaling via the RA receptor (RAR)/retinoid X receptor (RXR) complex contribute to Aldh1a2 expression. The RAR antagonist LE540 and the Sp1 inhibitor mithramycin A inhibited GM-CSF-induced Aldh1a2 expression in fms-related tyrosine kinase 3 ligand-generated bone marrow-derived DCs (BM-DCs). ERK and p38 MAPK inhibitors suppressed GM-CSF-induced nuclear translocation of Sp1 and Aldh1a2 expression. Sp1 and the RARα/RXRα complex bound to GC-rich Sp1-binding sites and an RA response element (RARE) half-site, respectively, near the TATA box in the mouse Aldh1a2 promoter. The DNA sequences around these sites were highly conserved among different species. In the presence of RA, ectopic expression of RARα/RXRα and Sp1 synergistically enhanced Aldh1a2 promoter-reporter activity. GM-CSF did not significantly induce Aldh1a2 expression in plasmacytoid DCs, peritoneal macrophages, or T cells, and the Aldh1a2 promoter in these cells was mostly unmethylated. These results suggest that GM-CSF/RA-induced RALDH2 expression in DCs requires cooperative binding of Sp1 and the RAR/RXR complex to the Aldh1a2 promoter, and can be regulated by a DNA methylation-independent mechanism.

Indexed as

Aldehyde OxidoreductasesAnimalsBase SequenceCells, CulturedChlorocebus aethiopsCOS CellsCpG IslandsDendritic CellsDibenzazepinesDNA MethylationDrug SynergismGene Expression Regulation, EnzymologicGranulocyte-Macrophage Colony-Stimulating FactorMAP Kinase Signaling SystemMice, Inbred C57BLMolecular Sequence DataAldehyde OxidoreductasesDibenzazepinesGranulocyte-Macrophage Colony-Stimulating FactorLE 540mithramycin APlicamycinRALDH2 protein, mouseReceptors, Retinoic AcidRetinoid X ReceptorsSp1 Transcription FactorTretinoin

Identifiers

PMID24788806
PMCPMC4008585

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.