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Rapamycin downregulates α-klotho in the kidneys of female rats with normal and reduced renal function
Both mTOR and α-klotho play a role in the pathophysiology of renal disease, influence mineral metabolism and participate in the aging process. The influence of mTOR inhibition by rapamycin on renal α-klotho expression is unknown. Rats with normal (controls) and reduced (Nx) renal function were treat...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10684065/ https://www.ncbi.nlm.nih.gov/pubmed/38015969 http://dx.doi.org/10.1371/journal.pone.0294791 |
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author | Espartero, Azahara Vidal, Angela Lopez, Ignacio Raya, Ana I. Rodriguez, Mariano Aguilera-Tejero, Escolastico Pineda, Carmen |
author_facet | Espartero, Azahara Vidal, Angela Lopez, Ignacio Raya, Ana I. Rodriguez, Mariano Aguilera-Tejero, Escolastico Pineda, Carmen |
author_sort | Espartero, Azahara |
collection | PubMed |
description | Both mTOR and α-klotho play a role in the pathophysiology of renal disease, influence mineral metabolism and participate in the aging process. The influence of mTOR inhibition by rapamycin on renal α-klotho expression is unknown. Rats with normal (controls) and reduced (Nx) renal function were treated with rapamycin, 1.3 mg/kg/day, for 22 days. The experiments were conducted with rats fed 0.6% P diet (NP) and 0.2% P diet (LP). Treatment with rapamycin promoted phosphaturia in control and Nx rats fed NP and LP. A decrease in FGF23 was identified in controls after treatment with rapamycin. In rats fed NP, rapamycin decreased mRNA α-klotho/GADPH ratio both in controls, 0.6±0.1 vs 1.1±0.1, p = 0.001, and Nx, 0.3±0.1 vs 0.7±0.1, p = 0.01. At the protein level, a significant reduction in α-klotho was evidenced after treatment with rapamycin both by Western Blot: 0.6±0.1 vs 1.0±0.1, p = 0.01, in controls, 0.7±0.1 vs 1.1±0.1, p = 0.02, in Nx; and by immunohistochemistry staining. Renal α-klotho was inversely correlated with urinary P excretion (r = -0.525, p = 0.0002). The decrease in α-klotho after treatment with rapamycin was also observed in rats fed LP. In conclusion, rapamycin increases phosphaturia and down-regulates α-klotho expression in rats with normal and decreased renal function. These effects can be observed in animals ingesting normal and low P diet. |
format | Online Article Text |
id | pubmed-10684065 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-106840652023-11-30 Rapamycin downregulates α-klotho in the kidneys of female rats with normal and reduced renal function Espartero, Azahara Vidal, Angela Lopez, Ignacio Raya, Ana I. Rodriguez, Mariano Aguilera-Tejero, Escolastico Pineda, Carmen PLoS One Research Article Both mTOR and α-klotho play a role in the pathophysiology of renal disease, influence mineral metabolism and participate in the aging process. The influence of mTOR inhibition by rapamycin on renal α-klotho expression is unknown. Rats with normal (controls) and reduced (Nx) renal function were treated with rapamycin, 1.3 mg/kg/day, for 22 days. The experiments were conducted with rats fed 0.6% P diet (NP) and 0.2% P diet (LP). Treatment with rapamycin promoted phosphaturia in control and Nx rats fed NP and LP. A decrease in FGF23 was identified in controls after treatment with rapamycin. In rats fed NP, rapamycin decreased mRNA α-klotho/GADPH ratio both in controls, 0.6±0.1 vs 1.1±0.1, p = 0.001, and Nx, 0.3±0.1 vs 0.7±0.1, p = 0.01. At the protein level, a significant reduction in α-klotho was evidenced after treatment with rapamycin both by Western Blot: 0.6±0.1 vs 1.0±0.1, p = 0.01, in controls, 0.7±0.1 vs 1.1±0.1, p = 0.02, in Nx; and by immunohistochemistry staining. Renal α-klotho was inversely correlated with urinary P excretion (r = -0.525, p = 0.0002). The decrease in α-klotho after treatment with rapamycin was also observed in rats fed LP. In conclusion, rapamycin increases phosphaturia and down-regulates α-klotho expression in rats with normal and decreased renal function. These effects can be observed in animals ingesting normal and low P diet. Public Library of Science 2023-11-28 /pmc/articles/PMC10684065/ /pubmed/38015969 http://dx.doi.org/10.1371/journal.pone.0294791 Text en © 2023 Espartero et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Espartero, Azahara Vidal, Angela Lopez, Ignacio Raya, Ana I. Rodriguez, Mariano Aguilera-Tejero, Escolastico Pineda, Carmen Rapamycin downregulates α-klotho in the kidneys of female rats with normal and reduced renal function |
title | Rapamycin downregulates α-klotho in the kidneys of female rats with normal and reduced renal function |
title_full | Rapamycin downregulates α-klotho in the kidneys of female rats with normal and reduced renal function |
title_fullStr | Rapamycin downregulates α-klotho in the kidneys of female rats with normal and reduced renal function |
title_full_unstemmed | Rapamycin downregulates α-klotho in the kidneys of female rats with normal and reduced renal function |
title_short | Rapamycin downregulates α-klotho in the kidneys of female rats with normal and reduced renal function |
title_sort | rapamycin downregulates α-klotho in the kidneys of female rats with normal and reduced renal function |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10684065/ https://www.ncbi.nlm.nih.gov/pubmed/38015969 http://dx.doi.org/10.1371/journal.pone.0294791 |
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