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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...

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Autores principales: Espartero, Azahara, Vidal, Angela, Lopez, Ignacio, Raya, Ana I., Rodriguez, Mariano, Aguilera-Tejero, Escolastico, Pineda, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
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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.
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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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