ArticleProceedings of the National Academy of Sciences of the United States of America2018
Interrelated role of Klotho and calcium-sensing receptor in parathyroid hormone synthesis and parathyroid hyperplasia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Case Report: Calcium sensing receptor gene gain of function mutations: a case series and report of 2 novel mutations.Frontiers in endocrinology · 2023Pooled it
- Autosomal Dominant Hypocalcemia Type 1: A Systematic Review.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Pooled it
- Parathyroid histology in normocalcemic and hypercalcemic primary hyperparathyroidism with hypercalciuric renal stones.Journal of the Endocrine Society · 2026Article
- Article
- Klotho in aging and diseases: molecular features, expressions, and functional implications.Molecular and cellular biochemistry · 2026Review
- Hypermethylation of the p16Acta histochemica et cytochemica · 2025Article
- Parathyroid glands exhibit reduced parenchymatic chief cells and increased extracellular collagen as a response to a long-term low-phosphorus diet in pigs.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Calcium-sensing receptor- and ADAM10-mediated klotho shedding is regulated by tetraspanin 5.FEBS letters · 2025Article
- Heterogeneous Transcriptional Landscapes in Human Sporadic Parathyroid Gland Tumors.International journal of molecular sciences · 2024Article
- KMT2A and chronic inflammation as potential drivers of sporadic parathyroid adenoma.Clinical and translational medicine · 2024Article
- Roles of Parathyroid Hormone and Fibroblast Growth Factor 23 in Advanced Chronic Kidney Disease.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- New insights into the role of Klotho in inflammation and fibrosis: molecular and cellular mechanisms.Frontiers in immunology · 2024Review
- Cellular and molecular mechanisms of the organogenesis and development, and function of the mammalian parathyroid gland.Cell and tissue research · 2023Review
- [MiR-301a-5p modulates parathyroid hormone secretion in secondary hyperparathyroidism possibly by regulating calcium-sensing receptor].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Roles of PTH and FGF23 in kidney failure: a focus on nonclassical effects.Clinical and experimental nephrology · 2023Review
- Inhibition of the calcium-sensing receptor by extracellular phosphate ions and by intracellular phosphorylation.Frontiers in physiology · 2023Review
- Neural Regeneration in Regenerative Endodontic Treatment: An Overview and Current Trends.International journal of molecular sciences · 2022Review
- Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Review
- Klotho in OsxSignal transduction and targeted therapy · 2022Article
- Integrated transcriptomic and proteomic analyses for the characterization of parathyroid oxyphil cells in uremic patients.Amino acids · 2022Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
The pathogenesis of parathyroid gland hyperplasia is poorly understood, and a better understanding is essential if there is to be improvement over the current strategies for prevention and treatment of secondary hyperparathyroidism. Here we investigate the specific role of Klotho expressed in the parathyroid glands (PTGs) in mediating parathyroid hormone (PTH) and serum calcium homeostasis, as well as the potential interaction between calcium-sensing receptor (CaSR) and Klotho. We generated mouse strains with PTG-specific deletion of Klotho and CaSR and dual deletion of both genes. We show that ablating CaSR in the PTGs increases PTH synthesis, that Klotho has a pivotal role in suppressing PTH in the absence of CaSR, and that CaSR together with Klotho regulates PTH biosynthesis and PTG growth. We utilized the tdTomato gene in our mice to visualize and collect PTGs to reveal an inhibitory function of Klotho on PTG cell proliferation. Chronic hypocalcemia and ex vivo PTG culture demonstrated an independent role for Klotho in mediating PTH secretion. Moreover, we identify an interaction between PTG-expressed CaSR and Klotho. These findings reveal essential and interrelated functions for CaSR and Klotho during parathyroid hyperplasia.
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