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(Pro)renin Receptor Regulates Phosphate Homeostasis in Rats via Releasing Fibroblast Growth Factor-23
Phosphate (Pi) is one of the basic necessities required for sustenance of life and its metabolism largely relies on excretory function of the kidney, a process chiefly under the endocrine control of bone-derived fibroblast growth factor 23 (FGF23). However, knowledge gap exists in understanding the...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874195/ https://www.ncbi.nlm.nih.gov/pubmed/35222071 http://dx.doi.org/10.3389/fphys.2022.784521 |
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author | Lu, Aihua Pu, Min Mo, Shiqi Su, Jiahui Hu, Jiajia Li, Chunling Wang, Weidong Yang, Tianxin |
author_facet | Lu, Aihua Pu, Min Mo, Shiqi Su, Jiahui Hu, Jiajia Li, Chunling Wang, Weidong Yang, Tianxin |
author_sort | Lu, Aihua |
collection | PubMed |
description | Phosphate (Pi) is one of the basic necessities required for sustenance of life and its metabolism largely relies on excretory function of the kidney, a process chiefly under the endocrine control of bone-derived fibroblast growth factor 23 (FGF23). However, knowledge gap exists in understanding the regulatory loop responsible for eliciting phophaturic response to Pi treatment. Here, we reported a novel role of (pro)renin receptor (PRR) in mediating phosphaturic response to Pi treatment via upregulation of FGF23 production. Male Sprague-Dawley rats were pretreated for 5 days via osmotic pump-driven infusion of a PRR antagonist PRO20 or vehicle, and then treated with high Pi (HP) solution as drinking fluid for the last 24 h. PRO20 reduced HP-induced Pi excretion by 42%, accompanied by blunted upregulation of circulating FGF23 and parathyroid hormone (PTH) and downregulation of renal Na/Pi-IIa expression. In cultured osteoblast cells, exposure to HP induced a 1.56-fold increase in FGF23 expression, which was blunted by PRO20 or siRNA against PRR. Together, these results suggest that activation of PRR promotes phosphaturic response through stimulation of FGF23 production and subsequent downregulation of renal Na/Pi-IIa expression. |
format | Online Article Text |
id | pubmed-8874195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88741952022-02-26 (Pro)renin Receptor Regulates Phosphate Homeostasis in Rats via Releasing Fibroblast Growth Factor-23 Lu, Aihua Pu, Min Mo, Shiqi Su, Jiahui Hu, Jiajia Li, Chunling Wang, Weidong Yang, Tianxin Front Physiol Physiology Phosphate (Pi) is one of the basic necessities required for sustenance of life and its metabolism largely relies on excretory function of the kidney, a process chiefly under the endocrine control of bone-derived fibroblast growth factor 23 (FGF23). However, knowledge gap exists in understanding the regulatory loop responsible for eliciting phophaturic response to Pi treatment. Here, we reported a novel role of (pro)renin receptor (PRR) in mediating phosphaturic response to Pi treatment via upregulation of FGF23 production. Male Sprague-Dawley rats were pretreated for 5 days via osmotic pump-driven infusion of a PRR antagonist PRO20 or vehicle, and then treated with high Pi (HP) solution as drinking fluid for the last 24 h. PRO20 reduced HP-induced Pi excretion by 42%, accompanied by blunted upregulation of circulating FGF23 and parathyroid hormone (PTH) and downregulation of renal Na/Pi-IIa expression. In cultured osteoblast cells, exposure to HP induced a 1.56-fold increase in FGF23 expression, which was blunted by PRO20 or siRNA against PRR. Together, these results suggest that activation of PRR promotes phosphaturic response through stimulation of FGF23 production and subsequent downregulation of renal Na/Pi-IIa expression. Frontiers Media S.A. 2022-02-11 /pmc/articles/PMC8874195/ /pubmed/35222071 http://dx.doi.org/10.3389/fphys.2022.784521 Text en Copyright © 2022 Lu, Pu, Mo, Su, Hu, Li, Wang and Yang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Lu, Aihua Pu, Min Mo, Shiqi Su, Jiahui Hu, Jiajia Li, Chunling Wang, Weidong Yang, Tianxin (Pro)renin Receptor Regulates Phosphate Homeostasis in Rats via Releasing Fibroblast Growth Factor-23 |
title | (Pro)renin Receptor Regulates Phosphate Homeostasis in Rats via Releasing Fibroblast Growth Factor-23 |
title_full | (Pro)renin Receptor Regulates Phosphate Homeostasis in Rats via Releasing Fibroblast Growth Factor-23 |
title_fullStr | (Pro)renin Receptor Regulates Phosphate Homeostasis in Rats via Releasing Fibroblast Growth Factor-23 |
title_full_unstemmed | (Pro)renin Receptor Regulates Phosphate Homeostasis in Rats via Releasing Fibroblast Growth Factor-23 |
title_short | (Pro)renin Receptor Regulates Phosphate Homeostasis in Rats via Releasing Fibroblast Growth Factor-23 |
title_sort | (pro)renin receptor regulates phosphate homeostasis in rats via releasing fibroblast growth factor-23 |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874195/ https://www.ncbi.nlm.nih.gov/pubmed/35222071 http://dx.doi.org/10.3389/fphys.2022.784521 |
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