ArticleThe Journal of clinical investigation2013
A nonclassical vitamin D receptor pathway suppresses renal fibrosis.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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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.
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Who cites it
72 citing papers in PubMed, 135 citations in OpenAlex.
- The effect of cholecalciferol supplementation on allograft function in incident kidney transplant recipients: A randomized controlled study.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Trial
- Insulin-sensitizing effects of vitamin D repletion mediated by adipocyte vitamin D receptor: Studies in humans and mice.Molecular metabolism · 2020Trial
- Trial
- The Role of Gut Microbiota in Liver Regeneration After Partial Hepatectomy: New Evidence From Animal and Human Studies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Association Between Vitamin D Deficiency and Systemic Outcomes in Patients with Glaucoma: A Real-World Cohort Study.Nutrients · 2026Article
- Paricalcitol Attenuates Bleomycin-induced Pulmonary Fibrosis: Insights from Immunohistochemical and Molecular Genetic Analysis.Endocrine, metabolic & immune disorders drug targets · 2026Article
- ECM remodeling in hypothyroidism-associated MAFLD: mechanisms, clinical relevance, and therapeutic targets.Frontiers in immunology · 2025Review
- Diabetic kidney disease: from pathogenesis to multimodal therapy-current evidence and future directions.Frontiers in medicine · 2025Review
- Nutritional insights into pulmonary fibrosis: a comprehensive review on the impact of vitamins.Frontiers in nutrition · 2025Review
- Cellular and Molecular Genetic Mechanisms of Lung Fibrosis Development and the Role of Vitamin D: A Review.International journal of molecular sciences · 2024Review
- Vitamin D Receptor Regulates Liver Regeneration After Partial Hepatectomy in Male Mice.Endocrinology · 2024Article
- Association between serum vitamin D and the risk of diabetic kidney disease in patients with type 2 diabetes.Frontiers in medicine · 2024Article
- TGF-β1 stimulation and VDR-dependent activation modulate calcitriol action on skeletal muscle fibroblasts and Smad signalling-associated fibrogenesis.Scientific reports · 2023Article
- Vitamin D and chronic kidney disease: Insights on lipid metabolism of tubular epithelial cell and macrophages in tubulointerstitial fibrosis.Frontiers in physiology · 2023Review
- Paricalcitol Improves the Angiopoietin/Tie-2 and VEGF/VEGFR2 Signaling Pathways in Adriamycin-Induced Nephropathy.Nutrients · 2022Article
- Effects of Hypocalcemic Vitamin D Analogs in the Expression of DNA Damage Induced in Minilungs from hESCs: Implications for Lung Fibrosis.International journal of molecular sciences · 2022Article
- The Role of Vitamin D in Diabetic Nephropathy: A Translational Approach.International journal of molecular sciences · 2022Review
- 25(OH)-Vitamin D alleviates neonatal infectious pneumonia via regulating TGFβ-mediated nuclear translocation mechanism of YAP/TAZ.Bioengineered · 2021Article
- Calcitriol Treatment Attenuates Uric Acid-Induced Kidney Injury via Super Oxide Dismutase-1 (SOD-1) Upregulation and Fibrosis ReductionIranian biomedical journal · 2021Article
- Transforming growth factor beta 1 (TGFβ1) plasmatic levels and haplotype structures in obesity: a role for TGFβ1 in steatosis development.Molecular biology reports · 2021Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The TGF-β superfamily comprises pleiotropic cytokines that regulate SMAD and non-SMAD signaling. TGF-β-SMAD signal transduction is known to be involved in tissue fibrosis, including renal fibrosis. Here, we found that 1,25-dihydroxyvitamin D3-bound [1,25(OH)2D3-bound] vitamin D receptor (VDR) specifically inhibits TGF-β-SMAD signal transduction through direct interaction with SMAD3. In mouse models of tissue fibrosis, 1,25(OH)2D3 treatment prevented renal fibrosis through the suppression of TGF-β-SMAD signal transduction. Based on the structure of the VDR-ligand complex, we generated 2 synthetic ligands. These ligands selectively inhibited TGF-β-SMAD signal transduction without activating VDR-mediated transcription and significantly attenuated renal fibrosis in mice. These results indicate that 1,25(OH)2D3-dependent suppression of TGF-β-SMAD signal transduction is independent of VDR-mediated transcriptional activity. In addition, these ligands did not cause hypercalcemia resulting from stimulation of the transcriptional activity of the VDR. Thus, our study provides a new strategy for generating chemical compounds that specifically inhibit TGF-β-SMAD signal transduction. Since TGF-β-SMAD signal transduction is reportedly involved in several disorders, our results will aid in the development of new drugs that do not cause detectable adverse effects, such as hypercalcemia.
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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.