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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2013
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oai:doaj.org-article:f170bbd4bec141d581755bf2c0aacf032021-11-18T08:39:54ZHyperlipidemia-associated renal damage decreases Klotho expression in kidneys from ApoE knockout mice.1932-620310.1371/journal.pone.0083713https://doaj.org/article/f170bbd4bec141d581755bf2c0aacf032013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24386260/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<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.Cristina SastreAlfonso Rubio-NavarroIrene BuendíaCarmen Gómez-GuerreroJulia BlancoSebastian MasJesús EgidoLuis Miguel Blanco-ColioAlberto OrtizJuan Antonio MorenoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e83713 (2013) |
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Medicine R Science Q 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 Hyperlipidemia-associated renal damage decreases Klotho expression in kidneys from ApoE knockout mice. |
| description |
<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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Cristina Sastre |
| title |
Hyperlipidemia-associated renal damage decreases Klotho expression in kidneys from ApoE knockout mice. |
| title_short |
Hyperlipidemia-associated renal damage decreases Klotho expression in kidneys from ApoE knockout mice. |
| title_full |
Hyperlipidemia-associated renal damage decreases Klotho expression in kidneys from ApoE knockout mice. |
| title_fullStr |
Hyperlipidemia-associated renal damage decreases Klotho expression in kidneys from ApoE knockout mice. |
| title_full_unstemmed |
Hyperlipidemia-associated renal damage decreases Klotho expression in kidneys from ApoE knockout mice. |
| title_sort |
hyperlipidemia-associated renal damage decreases klotho expression in kidneys from apoe knockout mice. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/f170bbd4bec141d581755bf2c0aacf03 |
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