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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...

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Autores principales: Cheng, Lijuan, Zhang, Lei, Yang, Jun, Hao, Lirong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2017
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.
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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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