ArticleJournal of the American Society of Nephrology : JASN2008
EGFR activation increases parathyroid hyperplasia and calcitriol resistance in kidney disease.
Article in Journal of the American Society of Nephrology : JASN, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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Who cites it
27 citing papers in PubMed, 67 citations in OpenAlex.
- Pre-Parathyroidectomy PTH as an Integrated Biomarker of Glandular Remodeling and Skeletal Turnover in Secondary Hyperparathyroidism.International journal of molecular sciences · 2026Review
- 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
- Role of Calcimimetics in Treating Bone and Mineral Disorders Related to Chronic Kidney Disease.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Molecular Mechanisms of Parathyroid Disorders in Chronic Kidney Disease.Metabolites · 2022Review
- Mechanism of calcitriol regulating parathyroid cells in secondary hyperparathyroidism.Frontiers in pharmacology · 2022Review
- Non-classical Vitamin D Actions for Renal Protection.Frontiers in medicine · 2021Review
- Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney Disease.International journal of molecular sciences · 2020Review
- PTH suppression by calcitriol does not predict off-target actions in experimental CKD.Pharmacology research & perspectives · 2020Article
- The Blockade of TACE-Dependent EGF Receptor Activation by Losartan-Erlotinib Combination Attenuates Renal Fibrosis Formation in 5/6-Nephrectomized Rats Under Vitamin D Deficiency.Frontiers in medicine · 2020Article
- Deficiency in the secreted protein Semaphorin3d causes abnormal parathyroid development in mice.The Journal of biological chemistry · 2019Article
- EGFR and C/EBP-β oncogenic signaling is bidirectional in human glioma and varies with the C/EBP-β isoform.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Phosphorylation of Ribosomal Protein S6 Mediates Mammalian Target of Rapamycin Complex 1-Induced Parathyroid Cell Proliferation in Secondary Hyperparathyroidism.Journal of the American Society of Nephrology : JASN · 2016Article
- Parathyroid-specific epidermal growth factor-receptor inactivation prevents uremia-induced parathyroid hyperplasia in mice.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2015Article
- The induction of C/EBPβ contributes to vitamin D inhibition of ADAM17 expression and parathyroid hyperplasia in kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2015Article
- Expression of p53, Ki67, epidermal growth factor receptor, transforming growth-factorα, and p21 in primary and secondary hyperparathyroidism.Indian journal of endocrinology and metabolism · 2014Article
- Lysophosphatidic acid (LPA) and its receptors: role in airway inflammation and remodeling.Biochimica et biophysica acta · 2013Review
- Diseases of the parathyroid gland in chronic kidney disease.Clinical and experimental nephrology · 2011Review
- Cyclooxygenase 2 promotes parathyroid hyperplasia in ESRD.Journal of the American Society of Nephrology : JASN · 2011Article
- Hormone response element binding proteins: novel regulators of vitamin D and estrogen signaling.Steroids · 2011Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Calcitriol, acting through vitamin D receptors (VDR) in the parathyroid, suppresses parathyroid hormone synthesis and cell proliferation. In secondary hyperparathyroidism (SH), VDR content is reduced as hyperplasia becomes more severe, limiting the efficacy of calcitriol. In a rat model of SH, activation of the EGF receptor (EGFR) by TGF-alpha is required for the development of parathyroid hyperplasia, but the relationship between EGFR activation and reduced VDR content is unknown. With the use of the same rat model, it was found that pharmacologic inhibition of EGFR activation with erlotinib prevented the upregulation of parathyroid TGF-alpha, the progression of growth, and the reduction of VDR. Increased TGF-alpha/EGFR activation induced the synthesis of liver-enriched inhibitory protein, a potent mitogen and the dominant negative isoform of the transcription factor CCAAT enhancer binding protein-beta, in human hyperplastic parathyroid glands and in the human epidermoid carcinoma cell line A431, which mimics hyperplastic parathyroid cells. Increases in liver-enriched inhibitory protein directly correlated with proliferating activity and, in A431 cells, reduced VDR expression by antagonizing CCAAT enhancer binding protein-beta transactivation of the VDR gene. Similarly, in nodular hyperplasia, which is the most severe form of SH and the most resistant to calcitriol therapy, higher TGF-alpha activation of the EGFR was associated with an 80% reduction in VDR mRNA levels. Thus, in SH, EGFR activation is the cause of both hyperplastic growth and VDR reduction and therefore influences the efficacy of therapy with calcitriol.
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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.