ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
RORα and ROR γ are expressed in human skin and serve as receptors for endogenously produced noncalcemic 20-hydroxy- and 20,23-dihydroxyvitamin D.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers.
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Who cites it
184 citing papers in PubMed, 266 citations in OpenAlex.
- Impact of topical emollient, steroids alone or combined with calcipotriol, on the immune infiltrate and clinical outcome in psoriasis.Experimental dermatology · 2022Trial
- Preclinical and clinical characterization of the RORγt inhibitor JNJ-61803534.Scientific reports · 2021Trial
- Vitamin D decreases tumor cell growth and invasiveness in primary malignant bone tumors in vitro.Journal of bone oncology · 2026Article
- Vitamin D and antimicrobial peptides in skin health and disease: Mechanisms and therapeutic potential.Biochemistry and biophysics reports · 2026Review
- Review
- Melatonin Regulates Arylhydrocarbon Receptor Mediated UVR-Induced Processes Related to Inflammation, Skin Aging and Carcinogenesis in Human Ex Vivo Skin.Experimental dermatology · 2026Article
- Inhibition of the RIPK4 enhances suppression of human melanoma growth through vitamin D signaling.Molecular and cellular endocrinology · 2025Article
- Melatonin and the Skin: Current Progress and Perspectives for Human Health.The Journal of investigative dermatology · 2025Review
- 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 · 2025Review
- The vitamin DAmerican journal of physiology. Cell physiology · 2025Article
- RORα fine-tunes the circadian control of hepatic triglyceride synthesis and gluconeogenesis.Scientific reports · 2025Article
- RORA Regulates Autophagy in Hair Follicle Stem Cells by Upregulating the Expression Level of theBiomolecules · 2025Article
- Melatonin-Mediated Circadian Rhythm Signaling Exhibits Bidirectional Regulatory Effects on the State of Hair Follicle Stem Cells.Biomolecules · 2025Article
- A Complex Interplay Between Melatonin and RORβ: RORβ is Unlikely a Putative Receptor for Melatonin as Revealed by Biophysical Assays.Molecular neurobiology · 2025Article
- The Role of Retinoic-Acid-Related Orphan Receptor (RORs) in Cellular Homeostasis.International journal of molecular sciences · 2024Review
- Evolutionary formation of melatonin and vitamin D in early life forms: insects take centre stage.Biological reviews of the Cambridge Philosophical Society · 2024Review
- Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin.The Journal of investigative dermatology · 2024Review
- New Sesquiterpenoids from the Mangrove-Derived FungusMarine drugs · 2024Article
- Effect of melatonin as a therapeutic strategy against intrauterine growth restriction: a mini-review of current state.Annals of medicine and surgery (2012) · 2024Review
- Relation of T Cell Profile with Vitamin D Receptor and Vitamin D-Binding Protein Gene Polymorphisms in Atopy.International journal of molecular sciences · 2024Article
124 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
RORα and RORγ are expressed in human skin cells that produce the noncalcemic 20-hydroxyvitamin D3 [20(OH)D3] and 20,23-dihydroxyvitamin D3 [20,23(OH)2D3]. Chinese hamster ovary (CHO) cells stably expressing a Tet-on RORα or RORγ expression vector and a ROR-responsive element (RORE)-LUC reporter, and a mammalian 2-hybrid model examining the interaction between the ligand binding domain (LBD) of RORα or RORγ with an LBD-interacting LXXLL-peptide, were used to study ROR-antagonist activities. These assays revealed that 20(OH)D3 and 20,23(OH)2D3 function as antagonists of RORα and RORγ. Moreover, 20(OH)D3 inhibited the activation of the promoter of the Bmal1 and G6pase genes, targets of RORα, and 20(OH)D3 and 20,23(OH)2D3 inhibited Il17 promoter activity in Jurkat cells overexpressing RORα or RORγ. Molecular modeling using crystal structures of the LBDs of RORα and RORγ revealed docking scores for 20(OH)D3, 20,23(OH)2D3 and 1,25(OH)2D3 similar to those of the natural ligands, predicting good binding to the receptor. Notably, 20(OH)D3, 20,23(OH)2D3, and 1,25(OH)2D3 inhibited RORE-mediated activation of a reporter in keratinocytes and melanoma cells and inhibited IL-17 production by immune cells. Our study identifies a novel signaling pathway, in which 20(OH)D3 and 20,23(OH)2D3 act as antagonists or inverse agonists of RORα and RORγ, that opens new possibilities for local (skin) or systemic regulation.-Slominski, A. T., Kim, T.-K., Takeda, Y., Janjetovic, Z., Broz˙yna, A. A., Skobowiat, C., Wang, J., Postlethwaite, A., Li, W., Tuckey, R. C., Jetten, A. M. RORα and ROR γ are expressed in human skin and serve as receptors for endogenously produced noncalcemic 20-hydroxy- and 20,23-dihydroxyvitamin D.
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Registered trials
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.