Mañana, JUEVES, 24 DE ABRIL, el sistema se apagará debido a tareas habituales de mantenimiento a partir de las 9 de la mañana. Lamentamos las molestias.
Hyperlipidemia-associated renal damage decreases Klotho expression in kidneys from ApoE knockout mice
Entity
UAM. Departamento de MedicinaPublisher
Public Library of ScienceDate
2013-12-30Citation
10.1371/journal.pone.0083713
PLoS One 8.12 (2013): e83713
ISSN
1932-6203DOI
10.1371/journal.pone.0083713Funded by
This work has been supported by grants from FIS (Programa Miguel Servet: CP10/00479) to JAM and ISCIII (Programa de Estabilizacio´n) and PI10/00234 to LMBC. Fundacio´n Conchita Ra´bago to CS and ARN. Ministry of Science (SAF2012/38830) and Sociedad Espan˜ola de Nefrologia to CGG. ISCIII and FEDER funds PS09/00447, Sociedad Espan˜ola de Nefrologia, ISCIII-RETIC REDinREN/RD06/0016, Comunidad de Madrid/CIFRA/S2010/BMD-2378 to AO, and ISCIII-Redes RECAVA (RD06/0014/0035) REDINREN (RD12/0021/), European Network (HEALTH F2-2008-200647), Euro Salud EUS2005-03565, cvREMOD, Fundacion Lilly, FRIAT and ISCIII fund PI10/00072 to JE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Project
Comunidad de Madrid. S2010/BMD-2378/CIFRAEditor's Version
http://dx.doi.org/10.1371/journal.pone.0083713Subjects
Cholesterol; Diet; Epithelial cells; Hyperlipidemia; Inflammation; Kidneys; Oxidative stress; Protein expression; MedicinaAbstract
Background: Klotho is a renal protein with anti-aging properties that is downregulated in conditions related to kidney injury. Hyperlipidemia accelerates the progression of renal damage, but the mechanisms of the deleterious effects of hyperlipidemia remain unclear.
Methods: We evaluated whether hyperlipidemia modulates Klotho expression in kidneys from C57BL/6 and hyperlipidemic apolipoprotein E knockout (ApoE KO) mice fed with a normal chow diet (ND) or a Western-type high cholesterol-fat diet (HC) for 5 to 10 weeks, respectively.
Results: In ApoE KO mice, the HC diet increased serum and renal cholesterol levels, kidney injury severity, kidney macrophage infiltration and inflammatory chemokine expression. A significant reduction in Klotho mRNA and protein expression was observed in kidneys from hypercholesteromic ApoE KO mice fed a HC diet as compared with controls, both at 5 and 10 weeks. In order to study the mechanism involved in Klotho down-regulation, murine tubular epithelial cells were treated with ox-LDL. Oxidized-LDL were effectively uptaken by tubular cells and decreased both Klotho mRNA and protein expression in a time- and dose-dependent manner in these cells. Finally, NF-κB and ERK inhibitors prevented ox-LDL-induced Klotho downregulation.
Conclusion: Our results suggest that hyperlipidemia-associated kidney injury decreases renal expression of Klotho. Therefore, Klotho could be a key element explaining the relationship between hyperlipidemia and aging with renal disease.
Files in this item
Google Scholar:Sastre, Cristina
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Rubio-Navarro, Alfonso
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Buendía, Irene
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Gómez Guerrero, Carmen
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Blanco, Julia
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Mas, Sebastián
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Egido, Jesús
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Blanco-Colio, Luis Miguel
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Ortiz Arduán, Alberto
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Moreno, Juan Antonio
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