Abstract | BACKGROUND: METHODS: In vivo studies were conducted in subtotally nephrectomized rats fed a normal or high P diet, with and without parathyroidectomy (PTX). PTX rats were supplemented with PTH(1-34) to achieve physiological serum PTH levels. In vitro studies were performed in rat aortic VSMCs cultured in control medium, calcifying medium (CM) or CM plus 10-7 versus 10-9 M PTH. RESULTS: Rats fed a high P diet had a significantly increased aortic calcium (Ca) content. Similarly, Ca deposition was higher in VSMCs exposed to CM. Both conditions were associated with increased RANKL and LGR4 and decreased OPG aorta expression and were exacerbated by high PTH. Silencing of LGR4 or parathyroid hormone receptor 1 (PTH1R) attenuated the high PTH-driven increases in Ca deposition. Furthermore, PTH1R silencing and pharmacological inhibition of protein kinase A (PKA), but not protein kinase C, prevented the increases in RANKL and LGR4 and decreased OPG. Treatment with PKA agonist corroborated that LGR4 regulation is a PTH/PKA-driven process. CONCLUSIONS: High PTH increases LGR4 and RANKL and decreases OPG expression in the aorta, thereby favouring VC. The hormone's direct pro-calcifying actions involve PTH1R binding and PKA activation.
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Authors | Natalia Carrillo-López, Laura Martínez-Arias, Cristina Alonso-Montes, Beatriz Martín-Carro, Julia Martín-Vírgala, Marta Ruiz-Ortega, José Luis Fernández-Martín, Adriana S Dusso, Minerva Rodriguez-García, Manuel Naves-Díaz, Jorge B Cannata-Andía, Sara Panizo |
Journal | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
(Nephrol Dial Transplant)
Vol. 36
Issue 4
Pg. 618-631
(03 29 2021)
ISSN: 1460-2385 [Electronic] England |
PMID | 33367746
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. |
Chemical References |
- Calcium-Regulating Hormones and Agents
- LGR4 receptor, rat
- Ligands
- NF-kappa B
- Osteoprotegerin
- Parathyroid Hormone
- RANK Ligand
- Receptor Activator of Nuclear Factor-kappa B
- Receptors, G-Protein-Coupled
- Tnfrsf11b protein, rat
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Topics |
- Animals
- Calcium-Regulating Hormones and Agents
(pharmacology)
- Gene Expression Regulation
(drug effects)
- Ligands
- Male
- Myocytes, Smooth Muscle
(metabolism)
- NF-kappa B
(metabolism)
- Osteoprotegerin
(genetics, metabolism)
- Parathyroid Hormone
(pharmacology)
- RANK Ligand
(genetics, metabolism)
- Rats
- Rats, Wistar
- Receptor Activator of Nuclear Factor-kappa B
(genetics, metabolism)
- Receptors, G-Protein-Coupled
(genetics, metabolism)
- Vascular Calcification
(metabolism)
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