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Up-regulation of liver Pcsk9 gene expression as a possible cause of hypercholesterolemia in experimental chronic renal failure
Dyslipidemia commonly present in patients with chronic kidney disease (CKD) has been recently linked to increased proprotein convertase subtilisin/kexin type 9 (PCSK9) serum concentration. We tested a hypothesis that increased liver PCSK9 biosynthesis could be partially responsible for the elevated...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737787/ https://www.ncbi.nlm.nih.gov/pubmed/26481479 http://dx.doi.org/10.1007/s11010-015-2590-0 |
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author | Sucajtys-Szulc, Elzbieta Szolkiewicz, Marek Swierczynski, Julian Rutkowski, Boleslaw |
author_facet | Sucajtys-Szulc, Elzbieta Szolkiewicz, Marek Swierczynski, Julian Rutkowski, Boleslaw |
author_sort | Sucajtys-Szulc, Elzbieta |
collection | PubMed |
description | Dyslipidemia commonly present in patients with chronic kidney disease (CKD) has been recently linked to increased proprotein convertase subtilisin/kexin type 9 (PCSK9) serum concentration. We tested a hypothesis that increased liver PCSK9 biosynthesis could be partially responsible for the elevated circulating PCSK9 level, and subsequently contribute to hypercholesterolemia observed in subjects with CKD. Rat model of chronic renal failure (CRF) was used in the study. Animals underwent a 5/6 nephrectomy or a sham operation. Liver expression of Pcsk9, sterol regulatory element-binding transcription factor 2 (Srebf-2), and β-actin were quantified by real-time RT-PCR. Liver protein levels of PCSK9, LDL-receptor (LDL-R), and SREBF-2 were analyzed using Western blotting. Serum PCSK9 concentration was estimated by immunoassay. Rats with an experimental CRF as compared to pair-fed and control ones were characterized by: (a) an up-regulation of liver Pcsk9 and Srebf-2 genes expression with parallel increase of serum PCSK9 concentration; (b) a decrease in liver LDL-R protein level, and (c) an increase of serum total and LDL-cholesterol concentrations. We also found significant correlations between serum creatinine and liver PCSK9 mRNA levels (r = 0.88, p < 0.001) and between serum creatinine and circulating PCSK9 levels (r = 0.73, p < 0.001). The results suggest that a rat model of CRF is associated with an increased liver Pcsk9 gene expression. The coordinated up-regulation of Pcsk9 and Srebf-2 genes expression suggests that SREBF-2 may play a key role in regulation of Pcsk9 gene expression, circulating PCSK9 level, and hypercholesterolemia in experimental CRF. |
format | Online Article Text |
id | pubmed-4737787 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-47377872016-02-09 Up-regulation of liver Pcsk9 gene expression as a possible cause of hypercholesterolemia in experimental chronic renal failure Sucajtys-Szulc, Elzbieta Szolkiewicz, Marek Swierczynski, Julian Rutkowski, Boleslaw Mol Cell Biochem Article Dyslipidemia commonly present in patients with chronic kidney disease (CKD) has been recently linked to increased proprotein convertase subtilisin/kexin type 9 (PCSK9) serum concentration. We tested a hypothesis that increased liver PCSK9 biosynthesis could be partially responsible for the elevated circulating PCSK9 level, and subsequently contribute to hypercholesterolemia observed in subjects with CKD. Rat model of chronic renal failure (CRF) was used in the study. Animals underwent a 5/6 nephrectomy or a sham operation. Liver expression of Pcsk9, sterol regulatory element-binding transcription factor 2 (Srebf-2), and β-actin were quantified by real-time RT-PCR. Liver protein levels of PCSK9, LDL-receptor (LDL-R), and SREBF-2 were analyzed using Western blotting. Serum PCSK9 concentration was estimated by immunoassay. Rats with an experimental CRF as compared to pair-fed and control ones were characterized by: (a) an up-regulation of liver Pcsk9 and Srebf-2 genes expression with parallel increase of serum PCSK9 concentration; (b) a decrease in liver LDL-R protein level, and (c) an increase of serum total and LDL-cholesterol concentrations. We also found significant correlations between serum creatinine and liver PCSK9 mRNA levels (r = 0.88, p < 0.001) and between serum creatinine and circulating PCSK9 levels (r = 0.73, p < 0.001). The results suggest that a rat model of CRF is associated with an increased liver Pcsk9 gene expression. The coordinated up-regulation of Pcsk9 and Srebf-2 genes expression suggests that SREBF-2 may play a key role in regulation of Pcsk9 gene expression, circulating PCSK9 level, and hypercholesterolemia in experimental CRF. Springer US 2015-10-19 2016 /pmc/articles/PMC4737787/ /pubmed/26481479 http://dx.doi.org/10.1007/s11010-015-2590-0 Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Article Sucajtys-Szulc, Elzbieta Szolkiewicz, Marek Swierczynski, Julian Rutkowski, Boleslaw Up-regulation of liver Pcsk9 gene expression as a possible cause of hypercholesterolemia in experimental chronic renal failure |
title | Up-regulation of liver Pcsk9 gene expression as a possible cause of hypercholesterolemia in experimental chronic renal failure |
title_full | Up-regulation of liver Pcsk9 gene expression as a possible cause of hypercholesterolemia in experimental chronic renal failure |
title_fullStr | Up-regulation of liver Pcsk9 gene expression as a possible cause of hypercholesterolemia in experimental chronic renal failure |
title_full_unstemmed | Up-regulation of liver Pcsk9 gene expression as a possible cause of hypercholesterolemia in experimental chronic renal failure |
title_short | Up-regulation of liver Pcsk9 gene expression as a possible cause of hypercholesterolemia in experimental chronic renal failure |
title_sort | up-regulation of liver pcsk9 gene expression as a possible cause of hypercholesterolemia in experimental chronic renal failure |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737787/ https://www.ncbi.nlm.nih.gov/pubmed/26481479 http://dx.doi.org/10.1007/s11010-015-2590-0 |
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