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Activation of peroxisome proliferator-activated receptor γ inhibits vascular calcification by upregulating Klotho
Cardiovascular diseases are common in patients with chronic kidney disease. One of the key symptoms is the calcification of the vascular smooth muscle cells (VSMCs), which is induced by dysregulated mineral metabolism with high circulating levels of inorganic phosphate (Pi) and calcium. Klotho, whic...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348673/ https://www.ncbi.nlm.nih.gov/pubmed/28352317 http://dx.doi.org/10.3892/etm.2016.3996 |
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author | Cheng, Lijuan Zhang, Lei Yang, Jun Hao, Lirong |
author_facet | Cheng, Lijuan Zhang, Lei Yang, Jun Hao, Lirong |
author_sort | Cheng, Lijuan |
collection | PubMed |
description | Cardiovascular diseases are common in patients with chronic kidney disease. One of the key symptoms is the calcification of the vascular smooth muscle cells (VSMCs), which is induced by dysregulated mineral metabolism with high circulating levels of inorganic phosphate (Pi) and calcium. Klotho, which was originally identified as an aging suppressor gene, has been shown to be associated with vascular calcification. Since Klotho was recently identified as a target for nuclear receptor peroxisome proliferator-activated receptor (PPAR) γ, the present study aimed to determine whether PPARγ regulates VSMC calcification through modulating the expression levels of Klotho. It was demonstrated that the expression of PPARγ was downregulated during Pi-induced VSMC calcification. In addition, treatment with PPARγ agonists inhibited the calcification and enhanced the expression of Klotho in VSMCs in a PPARγ-dependent manner. Of note, loss of Klotho expression by RNA interference abolished the ability of PPARγ activation to inhibit VSMC calcification. Furthermore, activation of Klotho as well as PPARγ inhibited the expression of Pi transporter 1/2 and reduced Pi influx into VSMCs. To the best of our knowledge, the present study was the first to demonstrate that PPARγ regulates VSMC calcification through activating Klotho. |
format | Online Article Text |
id | pubmed-5348673 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-53486732017-03-28 Activation of peroxisome proliferator-activated receptor γ inhibits vascular calcification by upregulating Klotho Cheng, Lijuan Zhang, Lei Yang, Jun Hao, Lirong Exp Ther Med Articles Cardiovascular diseases are common in patients with chronic kidney disease. One of the key symptoms is the calcification of the vascular smooth muscle cells (VSMCs), which is induced by dysregulated mineral metabolism with high circulating levels of inorganic phosphate (Pi) and calcium. Klotho, which was originally identified as an aging suppressor gene, has been shown to be associated with vascular calcification. Since Klotho was recently identified as a target for nuclear receptor peroxisome proliferator-activated receptor (PPAR) γ, the present study aimed to determine whether PPARγ regulates VSMC calcification through modulating the expression levels of Klotho. It was demonstrated that the expression of PPARγ was downregulated during Pi-induced VSMC calcification. In addition, treatment with PPARγ agonists inhibited the calcification and enhanced the expression of Klotho in VSMCs in a PPARγ-dependent manner. Of note, loss of Klotho expression by RNA interference abolished the ability of PPARγ activation to inhibit VSMC calcification. Furthermore, activation of Klotho as well as PPARγ inhibited the expression of Pi transporter 1/2 and reduced Pi influx into VSMCs. To the best of our knowledge, the present study was the first to demonstrate that PPARγ regulates VSMC calcification through activating Klotho. D.A. Spandidos 2017-02 2016-12-22 /pmc/articles/PMC5348673/ /pubmed/28352317 http://dx.doi.org/10.3892/etm.2016.3996 Text en Copyright: © Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Cheng, Lijuan Zhang, Lei Yang, Jun Hao, Lirong Activation of peroxisome proliferator-activated receptor γ inhibits vascular calcification by upregulating Klotho |
title | Activation of peroxisome proliferator-activated receptor γ inhibits vascular calcification by upregulating Klotho |
title_full | Activation of peroxisome proliferator-activated receptor γ inhibits vascular calcification by upregulating Klotho |
title_fullStr | Activation of peroxisome proliferator-activated receptor γ inhibits vascular calcification by upregulating Klotho |
title_full_unstemmed | Activation of peroxisome proliferator-activated receptor γ inhibits vascular calcification by upregulating Klotho |
title_short | Activation of peroxisome proliferator-activated receptor γ inhibits vascular calcification by upregulating Klotho |
title_sort | activation of peroxisome proliferator-activated receptor γ inhibits vascular calcification by upregulating klotho |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348673/ https://www.ncbi.nlm.nih.gov/pubmed/28352317 http://dx.doi.org/10.3892/etm.2016.3996 |
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