Hyperlipidemia-associated renal damage decreases Klotho expression in kidneys from ApoE knockout mice.

<h4>Background</h4>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.<h4>Metho...

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Autores principales: Cristina Sastre, Alfonso Rubio-Navarro, Irene Buendía, Carmen Gómez-Guerrero, Julia Blanco, Sebastian Mas, Jesús Egido, Luis Miguel Blanco-Colio, Alberto Ortiz, Juan Antonio Moreno
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/f170bbd4bec141d581755bf2c0aacf03
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Sumario:<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.