Evidence map›Paper›PMID 28900196›Full record

ArticleScientific reports2017

Characterization of a new pathway that activates lumisterol in vivo to biologically active hydroxylumisterols.

Andrzej T Slominski, Tae-Kang Kim, Judith V Hobrath, Zorica Janjetovic, Allen S W Oak, Arnold Postlethwaite, Zongtao Lin, Wei Li, Yukimasa Takeda, Anton M Jetten and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
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

55 citing papers in PubMed, 80 citations in OpenAlex.

  1. Trial
  2. Article
  3. Beneficial health effects of ultraviolet radiation: expert review and conference report.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2025
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  7. Evolutionary formation of melatonin and vitamin D in early life forms: insects take centre stage.Biological reviews of the Cambridge Philosophical Society · 2024
    Review
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  9. Review
  10. Review
  11. Photo-neuro-immuno-endocrinology: How the ultraviolet radiation regulates the body, brain, and immune system.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy.International journal of molecular sciences · 2022
    Review
  17. Metabolic activation of tachysterolFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  18. Article
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  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

11 authors at 6 institutions in 3 countries.

Andrzej T SlominskiDepartment of Dermatology, VA Medical Center, Birmingham, AL, 35249, USA. aslominski@uabmc.edu.ORCID 0000-0001-8963-3995
Tae-Kang KimDepartment of Dermatology, VA Medical Center, Birmingham, AL, 35249, USA.
Judith V HobrathDrug Discovery Unit, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, United Kingdom.
Zorica JanjetovicDepartment of Dermatology, VA Medical Center, Birmingham, AL, 35249, USA.
Allen S W OakDepartment of Dermatology, VA Medical Center, Birmingham, AL, 35249, USA.
Arnold PostlethwaiteDepartment of Medicine, Division of Rheumatology and Connective Tissue Diseases, University of Tennessee HSC, and Memphis VA Medical Center, Memphis, TN, 38163, USA.
Zongtao LinDepartment of Pharmaceutical Sciences, University of Tennessee HSC, Memphis, TN, 38163, USA.ORCID 0000-0002-6017-338X
Wei LiDepartment of Pharmaceutical Sciences, University of Tennessee HSC, Memphis, TN, 38163, USA.
Yukimasa TakedaCell Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, 27709, USA.
Anton M JettenCell Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, 27709, USA.ORCID 0000-0003-0954-4445
Robert C TuckeySchool of Molecular Sciences, The University of Western Australia, Perth, WA, Australia.
Birmingham VA Medical Center · USNational Institutes of Health · USUniversity of Tennessee Health Science Center · USMemphis VA Medical Center · USThe University of Western Australia · AUUniversity of Dundee · GB

Funding

Nuclear receptors--Action, functions, &roles in diseaseZ01ES101586 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI JETTEN, ANTON M · 2003 to 2008
$3.2M
Significance of metabolic activation of lumisterol in the skinR01AR071189 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SLOMINSKI, ANDRZEJ T · 2017 to 2021
$1.6M
Role of Exogenous Melatonin in Skin BiologyR01AR056666 · NIAMS · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI SLOMINSKI, ANDRZEJ T · 2011 to 2015
$1.6M
Mechanism of action of 20-hydroxyvitamin D3 in dermal fibroblastsR21AR066505 · NIAMS · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI SLOMINSKI, ANDRZEJ T · 2014 to 2015
$355k
Discovery of tissue-selective, nonhypercalcemic VDR modulators for RA treatmentR21AR063242 · NIAMS · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI LI, WEI, MILLER, DUANE D · 2013 to 2014
$351k
Acquisition of a Q-TOF Mass SpectrometerS10OD010678 · OD · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI LI, WEI · 2012 to 2012
$325k
Acquisition of a 400MHz Solution NMR System with an AutosamplerS10RR026377 · NCRR · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI LI, WEI · 2010 to 2010
$253k
The Vitamin D-Gelsolin-S1P Axis in Rheumatoid ArthritisI01CX001400 · VA · MEMPHIS VA MEDICAL CENTER · PI POSTLETHWAITE, ARNOLD E · 2017 to 2020
–
Program Project for Mechanisms and Treatment of ArthritisIP1BX001607 · VA · MEMPHIS VA MEDICAL CENTER · PI BRAND, DAVID D., POSTLETHWAITE, ARNOLD E · 2013 to 2016
–
BLRD VA IP1 BX001607CSRD VA I01 CX001400Intramural NIH HHS Z01 ES101586NCRR NIH HHS S10 RR026377NIAMS NIH HHS R01 AR056666NIAMS NIH HHS R01 AR071189NIAMS NIH HHS R21 AR063242NIAMS NIH HHS R21 AR066505NIH HHS S10 OD010678
6 · The paper itself

Abstract

Using LC/qTOF-MS we detected lumisterol, 20-hydroxylumisterol, 22-hydroxylumisterol, 24-hydroxylumisterol, 20,22-dihydroxylumisterol, pregnalumisterol, 17-hydroxypregnalumisterol and 17,20-dihydroxypregnalumisterol in human serum and epidermis, and the porcine adrenal gland. The hydroxylumisterols inhibited proliferation of human skin cells in a cell type-dependent fashion with predominant effects on epidermal keratinocytes. They also inhibited melanoma proliferation in both monolayer and soft agar. 20-Hydroxylumisterol stimulated the expression of several genes, including those associated with keratinocyte differentiation and antioxidative responses, while inhibiting the expression of others including RORA and RORC. Molecular modeling and studies on VDRE-transcriptional activity excludes action through the genomic site of the VDR. However, their favorable interactions with the A-pocket in conjunction with VDR translocation studies suggest they may act on this non-genomic VDR site. Inhibition of RORα and RORγ transactivation activities in a Tet-on CHO cell reporter system, RORα co-activator assays and inhibition of (RORE)-LUC reporter activity in skin cells, in conjunction with molecular modeling, identified RORα and RORγ as excellent receptor candidates for the hydroxylumisterols. Thus, we have discovered a new biologically relevant, lumisterogenic pathway, the metabolites of which display biological activity. This opens a new area of endocrine research on the effects of the hydroxylumisterols on different pathways in different cells and the mechanisms involved.

Indexed as

Metabolic Networks and PathwaysAnimalsBiomarkersCell Line, TumorChromatography, LiquidDose-Response Relationship, DrugEpidermisErgosterolHumansKeratinocytesModels, MolecularMolecular ConformationMolecular StructureNuclear Receptor Subfamily 1, Group F, Member 3Receptors, CalcitriolSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationBiomarkersErgosterolNuclear Receptor Subfamily 1, Group F, Member 3Receptors, Calcitriol

Identifiers

PMID28900196
PMCPMC5595834
OpenAlexW2751533291

What OpenQuestion holds

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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.