ArticleEndocrinology2021
Antifibrogenic Activities of CYP11A1-derived Vitamin D3-hydroxyderivatives Are Dependent on RORγ.
Article in Endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Serum vitamin D levels and acute kidney injury: a systemic review and meta-analysis.Scientific reports · 2022Pooled it
- Vitamin D as a Regulator of the Biological Clock-Implications for Circadian-Metabolic Dysregulation.International journal of molecular sciences · 2026Review
- Plant-Derived Agents and Systemic Sclerosis: A Systematic Review of Therapeutic Potential and Molecular Mechanisms.Current issues in molecular biology · 2026Review
- Regulatory role of vitamin DScientific reports · 2025Article
- Therapeutic Use of Integrin Signaling in Melanoma Cells: Physical Link with the Extracellular Matrix (ECM).Cancers · 2025Review
- The vitamin DAmerican journal of physiology. Cell physiology · 2025Article
- The Role of Retinoic-Acid-Related Orphan Receptor (RORs) in Cellular Homeostasis.International journal of molecular sciences · 2024Review
- Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin.The Journal of investigative dermatology · 2024Review
- Antioxidant Functions of Vitamin D and CYP11A1-Derived Vitamin D, Tachysterol, and Lumisterol Metabolites: Mechanisms, Clinical Implications, and Future Directions.Antioxidants (Basel, Switzerland) · 2024Review
- Review
- Article
- Synthetic Nucleic Acid Antigens in Localized Scleroderma.International journal of molecular sciences · 2023Article
- Novel CYP11A1-Derived Vitamin D and Lumisterol Biometabolites for the Management of COVID-19.Nutrients · 2022Review
- Vitamin D in Systemic Sclerosis: A Review.Nutrients · 2022Review
- Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy.International journal of molecular sciences · 2022Review
- Metabolic activation of tachysterolFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- CYP11A1‑derived vitamin D hydroxyderivatives as candidates for therapy of basal and squamous cell carcinomas.International journal of oncology · 2022Article
- Chemical synthesis, biological activities and action on nuclear receptors of 20S(OH)DBioorganic chemistry · 2022Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Previous studies showed that noncalcemic 20(OH)D3, a product of CYP11A1 action on vitamin D3, has antifibrotic activity in human dermal fibroblasts and in a bleomycin mouse model of scleroderma. In this study, we tested the role of retinoic acid-related orphan receptor γ (RORγ), which is expressed in skin, in the action of CYP11A1-derived secosteroids using murine fibroblasts isolated from the skin of wild-type (RORγ +/+), knockout (RORγ -/-), and heterozygote (RORγ +/-) mice. CYP11A1-derived 20(OH)D3, 20,23(OH)2D3, 1,20(OH)2D3, and 1,20,23(OH)3D3 inhibited proliferation of RORγ +/+ fibroblasts in a dose-dependent manner with a similar potency to 1,25(OH)2D3. Surprisingly, this effect was reversed in RORγ +/- and RORγ -/- fibroblasts, with the most pronounced stimulatory effect seen in RORγ -/- fibroblasts. All analogs tested inhibited TGF-β1-induced collagen synthesis in RORγ +/+ fibroblasts and the expression of other fibrosis-related genes. This effect was curtailed or reversed in RORγ -/- fibroblasts. These results show that the antiproliferative and antifibrotic activities of the vitamin D hydroxy derivatives are dependent on a functional RORγ. The dramatic changes in the transcriptomes of fibroblasts of RORγ -/- versus wild-type mice following treatment with 20(OH)D3 or 1,20(OH)2D3 provide a molecular basis to explain, at least in part, the observed phenotypic differences.
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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.