ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2015
The induction of C/EBPβ contributes to vitamin D inhibition of ADAM17 expression and parathyroid hyperplasia in kidney disease.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- The role of nutritional vitamin D on microinflammation and nutritional status in maintenance hemodialysis patients: a meta-analysis of randomized controlled trials.Frontiers in nutrition · 2026Pooled it
- Combination therapy with nutritional vitamin D and calcimimetics in secondary hyperparathyroidism: a mechanism-based approach to restoring PTH regulation.Frontiers in nutrition · 2026Review
- Current Controversies on Adequate Circulating Vitamin D Levels in CKD.International journal of molecular sciences · 2025Review
- Acute hyperglycemia induces podocyte apoptosis by monocyte TNF-α release, a process attenuated by vitamin D and GLP-1 receptor agonists.The Journal of steroid biochemistry and molecular biology · 2025Article
- Oral Administration of Vitamin D3 Prevents Corneal Damage in a Knock-Out Mouse Model of Sjögren's Syndrome.Biomedicines · 2023Article
- Vitamin D Deficiency Reduces Postthyroidectomy Protracted Hypoparathyroidism Risk. Is Gland Preconditioning Possible?Journal of the Endocrine Society · 2022Article
- Vitamin D and the Kidney: Two Players, One Console.International journal of molecular sciences · 2022Review
- Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia.Nutrients · 2022Article
- Metadichol®: A Novel Nanolipid Formulation That Inhibits SARS-CoV-2 and a Multitude of Pathological Viruses In Vitro.BioMed research international · 2022Article
- Endothelial ADAM17 Expression in the Progression of Kidney Injury in an Obese Mouse Model of Pre-Diabetes.International journal of molecular sciences · 2021Article
- ADAMs family in kidney physiology and pathology.EBioMedicine · 2021Review
- Key metalloproteinase-mediated pathways in the kidney.Nature reviews. Nephrology · 2021Review
- Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics.Nutrients · 2021Observational
- Contribution of ADAM17 and related ADAMs in cardiovascular diseases.Cellular and molecular life sciences : CMLS · 2021Review
- A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor.Pharmacology & therapeutics · 2021Review
- Non-classical Vitamin D Actions for Renal Protection.Frontiers in medicine · 2021Review
- Vitamin D-Induced Molecular Mechanisms to Potentiate Cancer Therapy and to Reverse Drug-Resistance in Cancer Cells.Nutrients · 2020Review
- Vitamin D and Its Potential Interplay With Pain Signaling Pathways.Frontiers in immunology · 2020Review
- Barley-ß-glucans reduce systemic inflammation, renal injury and aortic calcification through ADAM17 and neutral-sphingomyelinase2 inhibition.Scientific reports · 2019Article
- Histone demethylase KDM5A is transactivated by the transcription factor C/EBPβ and promotes preadipocyte differentiation by inhibiting Wnt/β-catenin signaling.The Journal of biological chemistry · 2019Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIn secondary hyperparathyroidism (SHPT), enhanced parathyroid levels of transforming growth factor-α (TGFα) increase EGF receptor (EGFR) activation causing parathyroid hyperplasia, high parathyroid hormone (PTH) and also reductions in vitamin D receptor (VDR) that limit vitamin D suppression of SHPT. Since anti-EGFR therapy is not an option in human SHPT, we evaluated ADAM17 as a therapeutic target to suppress parathyroid hyperplasia because ADAM17 is required to release mature TGFα, the most potent EGFR-activating ligand.
methodsComputer analysis of the ADAM17 promoter identified TGFα and C/EBPβ as potential regulators of the ADAM17 gene. Their regulation of ADAM17 expression, TGFα/EGFR-driven growth and parathyroid gland (PTG) enlargement were assessed in promoter-reporter assays in A431 cells and corroborated in rat and human SHPT, using erlotinib as anti-EGFR therapy to suppress TGFα signals, active vitamin D to induce C/EBPβ or the combination.
resultsWhile TGFα induced ADAM17-promoter activity by 2.2-fold exacerbating TGFα/EGFR-driven growth, ectopic C/EBPβ expression completely prevented this vicious synergy. Accordingly, in advanced human SHPT, parathyroid ADAM17 levels correlated directly with TGFα and inversely with C/EBPβ. Furthermore, combined erlotinib + calcitriol treatment suppressed TGFα/EGFR-cell growth and PTG enlargement more potently than erlotinib in part through calcitriol induction of C/EBPβ to inhibit ADAM17-promoter activity, mRNA and protein. Importantly, in rat SHPT, the correction of vitamin D deficiency effectively reversed the resistance to paricalcitol induction of C/EBPβ to suppress ADAM17 expression and PTG enlargement, reducing PTH by 50%.
conclusionIn SHPT, correction of vitamin D and calcitriol deficiency induces parathyroid C/EBPβ to efficaciously attenuate the severe ADAM17/TGFα synergy, which drives PTG enlargement and high PTH.
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