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High sodium reduced the expression of PTH1R and Klotho by inhibiting 1,25(OH)(2)D(3) synthesis in cultured proximal tubule epithelial cells

BACKGROUND: The proximal tubule is the sensing site of sodium and phosphate and the main place for the synthesis and metabolism of 1,25(OH)(2)D(3). We aimed to investigate the effects of high sodium on the synthesis and function of active vitamin D and local phosphate regulation in proximal tubular...

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Autores principales: Gu, Jie, Shi, Jialin, Chen, Xujiao, Mao, Jianping, You, Huaizhou, Chen, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347055/
https://www.ncbi.nlm.nih.gov/pubmed/35928745
http://dx.doi.org/10.21037/atm-21-5910
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author Gu, Jie
Shi, Jialin
Chen, Xujiao
Mao, Jianping
You, Huaizhou
Chen, Jing
author_facet Gu, Jie
Shi, Jialin
Chen, Xujiao
Mao, Jianping
You, Huaizhou
Chen, Jing
author_sort Gu, Jie
collection PubMed
description BACKGROUND: The proximal tubule is the sensing site of sodium and phosphate and the main place for the synthesis and metabolism of 1,25(OH)(2)D(3). We aimed to investigate the effects of high sodium on the synthesis and function of active vitamin D and local phosphate regulation in proximal tubular epithelial cells. METHODS: Human proximal tubule epithelial (HK-2) cells were treated with different concentrations of sodium/phosphate. The expression of 1α-OHase and 24-OHase was determined. Liquid chromatography/mass spectrometry (LC/MS) and enzyme-linked immunosorbent assay (ELISA) were used to detect the levels of 1,25(OH)(2)D(3.) RNA sequencing and bioinformatics analysis was used to probe into the possible pathways. Chromatin samples were immunoprecipitated with antibodies against parathyroid receptor 1 (PTH1R) and Klotho. RESULTS: We found that high sodium decreased the expression of 1,25(OH)(2)D(3) by reducing 1α-OHase and 24-OHase, reduced the expression of PTH1R and Klotho, and increased the intracellular calcium concentration. These effects were reversed by sodium phosphate transporter inhibitor, sodium hydrogen transporter inhibitor, and a chelator of the extracellular calcium, whereas enhanced by ouabain. Vitamin D receptor (VDR) agonists significantly increased the recruitment of VDR to the vitamin D response element (VDRE) of PTH1R and Klotho promoter, thus increasing the expression of PTH1R and Klotho. CONCLUSIONS: High sodium can decrease the synthesis of active vitamin D in the proximal tubules, affect the gene regulation of 1,25(OH)(2)D(3)/VDR, and significantly reduce the expression of PTH1R and Klotho. It revealed the influence of a high-sodium diet on mineral metabolism and the core role of vitamin D in kidney mineral metabolism.
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spelling pubmed-93470552022-08-03 High sodium reduced the expression of PTH1R and Klotho by inhibiting 1,25(OH)(2)D(3) synthesis in cultured proximal tubule epithelial cells Gu, Jie Shi, Jialin Chen, Xujiao Mao, Jianping You, Huaizhou Chen, Jing Ann Transl Med Original Article BACKGROUND: The proximal tubule is the sensing site of sodium and phosphate and the main place for the synthesis and metabolism of 1,25(OH)(2)D(3). We aimed to investigate the effects of high sodium on the synthesis and function of active vitamin D and local phosphate regulation in proximal tubular epithelial cells. METHODS: Human proximal tubule epithelial (HK-2) cells were treated with different concentrations of sodium/phosphate. The expression of 1α-OHase and 24-OHase was determined. Liquid chromatography/mass spectrometry (LC/MS) and enzyme-linked immunosorbent assay (ELISA) were used to detect the levels of 1,25(OH)(2)D(3.) RNA sequencing and bioinformatics analysis was used to probe into the possible pathways. Chromatin samples were immunoprecipitated with antibodies against parathyroid receptor 1 (PTH1R) and Klotho. RESULTS: We found that high sodium decreased the expression of 1,25(OH)(2)D(3) by reducing 1α-OHase and 24-OHase, reduced the expression of PTH1R and Klotho, and increased the intracellular calcium concentration. These effects were reversed by sodium phosphate transporter inhibitor, sodium hydrogen transporter inhibitor, and a chelator of the extracellular calcium, whereas enhanced by ouabain. Vitamin D receptor (VDR) agonists significantly increased the recruitment of VDR to the vitamin D response element (VDRE) of PTH1R and Klotho promoter, thus increasing the expression of PTH1R and Klotho. CONCLUSIONS: High sodium can decrease the synthesis of active vitamin D in the proximal tubules, affect the gene regulation of 1,25(OH)(2)D(3)/VDR, and significantly reduce the expression of PTH1R and Klotho. It revealed the influence of a high-sodium diet on mineral metabolism and the core role of vitamin D in kidney mineral metabolism. AME Publishing Company 2022-05 /pmc/articles/PMC9347055/ /pubmed/35928745 http://dx.doi.org/10.21037/atm-21-5910 Text en 2022 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Original Article
Gu, Jie
Shi, Jialin
Chen, Xujiao
Mao, Jianping
You, Huaizhou
Chen, Jing
High sodium reduced the expression of PTH1R and Klotho by inhibiting 1,25(OH)(2)D(3) synthesis in cultured proximal tubule epithelial cells
title High sodium reduced the expression of PTH1R and Klotho by inhibiting 1,25(OH)(2)D(3) synthesis in cultured proximal tubule epithelial cells
title_full High sodium reduced the expression of PTH1R and Klotho by inhibiting 1,25(OH)(2)D(3) synthesis in cultured proximal tubule epithelial cells
title_fullStr High sodium reduced the expression of PTH1R and Klotho by inhibiting 1,25(OH)(2)D(3) synthesis in cultured proximal tubule epithelial cells
title_full_unstemmed High sodium reduced the expression of PTH1R and Klotho by inhibiting 1,25(OH)(2)D(3) synthesis in cultured proximal tubule epithelial cells
title_short High sodium reduced the expression of PTH1R and Klotho by inhibiting 1,25(OH)(2)D(3) synthesis in cultured proximal tubule epithelial cells
title_sort high sodium reduced the expression of pth1r and klotho by inhibiting 1,25(oh)(2)d(3) synthesis in cultured proximal tubule epithelial cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347055/
https://www.ncbi.nlm.nih.gov/pubmed/35928745
http://dx.doi.org/10.21037/atm-21-5910
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