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Inorganic Phosphate Accelerates the Migration of Vascular Smooth Muscle Cells: Evidence for the Involvement of miR-223

BACKGOUND: An elevated serum inorganic phosphate (Pi) level is a major risk factor for kidney disease and downstream vascular complications. We focused on the effect of Pi levels on human aortic vascular smooth muscle cells (VSMCs), with an emphasis on the role of microRNAs (miRNAs). METHODOLOGY/PRI...

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Autores principales: Rangrez, Ashraf Yusuf, M'Baya-Moutoula, Eléonore, Metzinger-Le Meuth, Valérie, Hénaut, Lucie, Djelouat, Mohamed Seif el Islam, Benchitrit, Joyce, Massy, Ziad A., Metzinger, Laurent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475714/
https://www.ncbi.nlm.nih.gov/pubmed/23094093
http://dx.doi.org/10.1371/journal.pone.0047807
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author Rangrez, Ashraf Yusuf
M'Baya-Moutoula, Eléonore
Metzinger-Le Meuth, Valérie
Hénaut, Lucie
Djelouat, Mohamed Seif el Islam
Benchitrit, Joyce
Massy, Ziad A.
Metzinger, Laurent
author_facet Rangrez, Ashraf Yusuf
M'Baya-Moutoula, Eléonore
Metzinger-Le Meuth, Valérie
Hénaut, Lucie
Djelouat, Mohamed Seif el Islam
Benchitrit, Joyce
Massy, Ziad A.
Metzinger, Laurent
author_sort Rangrez, Ashraf Yusuf
collection PubMed
description BACKGOUND: An elevated serum inorganic phosphate (Pi) level is a major risk factor for kidney disease and downstream vascular complications. We focused on the effect of Pi levels on human aortic vascular smooth muscle cells (VSMCs), with an emphasis on the role of microRNAs (miRNAs). METHODOLOGY/PRINCIPAL FINDINGS: Exposure of human primary VSMCs in vitro to pathological levels of Pi increased calcification, migration rate and concomitantly reduced cell proliferation and the amount of the actin cytoskeleton. These changes were evidenced by significant downregulation of miRNA-143 (miR-143) and miR-145 and concomitant upregulation of their targets and key markers in synthetic VSMCs, such as Krüppel-like factors−4 and −5 and versican. Interestingly, we also found that miR-223 (a marker of muscle damage and a key factor in osteoclast differentiation) is expressed in VSMCs and is significantly upregulated in Pi-treated cells. Over-expressing miR-223 in VSMCs increased proliferation and markedly enhanced VSMC migration. Additionally, we found that the expression of two of the known miR-223 targets, Mef2c and RhoB, was highly reduced in Pi treated as well as miR-223 over-expressing VSMCs. To complement these in vitro findings, we also observed significant downregulation of miR-143 and miR-145 and upregulation of miR-223 in aorta samples collected from ApoE knock-out mice, which display vascular calcification. CONCLUSIONS/SIGNIFICANCE: Our results suggest that (i) high levels of Pi increase VSMC migration and calcification, (ii) altered expression levels of miR-223 could play a part in this process and (iii) miR-223 is a potential new biomarker of VSMC damage.
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spelling pubmed-34757142012-10-23 Inorganic Phosphate Accelerates the Migration of Vascular Smooth Muscle Cells: Evidence for the Involvement of miR-223 Rangrez, Ashraf Yusuf M'Baya-Moutoula, Eléonore Metzinger-Le Meuth, Valérie Hénaut, Lucie Djelouat, Mohamed Seif el Islam Benchitrit, Joyce Massy, Ziad A. Metzinger, Laurent PLoS One Research Article BACKGOUND: An elevated serum inorganic phosphate (Pi) level is a major risk factor for kidney disease and downstream vascular complications. We focused on the effect of Pi levels on human aortic vascular smooth muscle cells (VSMCs), with an emphasis on the role of microRNAs (miRNAs). METHODOLOGY/PRINCIPAL FINDINGS: Exposure of human primary VSMCs in vitro to pathological levels of Pi increased calcification, migration rate and concomitantly reduced cell proliferation and the amount of the actin cytoskeleton. These changes were evidenced by significant downregulation of miRNA-143 (miR-143) and miR-145 and concomitant upregulation of their targets and key markers in synthetic VSMCs, such as Krüppel-like factors−4 and −5 and versican. Interestingly, we also found that miR-223 (a marker of muscle damage and a key factor in osteoclast differentiation) is expressed in VSMCs and is significantly upregulated in Pi-treated cells. Over-expressing miR-223 in VSMCs increased proliferation and markedly enhanced VSMC migration. Additionally, we found that the expression of two of the known miR-223 targets, Mef2c and RhoB, was highly reduced in Pi treated as well as miR-223 over-expressing VSMCs. To complement these in vitro findings, we also observed significant downregulation of miR-143 and miR-145 and upregulation of miR-223 in aorta samples collected from ApoE knock-out mice, which display vascular calcification. CONCLUSIONS/SIGNIFICANCE: Our results suggest that (i) high levels of Pi increase VSMC migration and calcification, (ii) altered expression levels of miR-223 could play a part in this process and (iii) miR-223 is a potential new biomarker of VSMC damage. Public Library of Science 2012-10-18 /pmc/articles/PMC3475714/ /pubmed/23094093 http://dx.doi.org/10.1371/journal.pone.0047807 Text en © 2012 Rangrez et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Rangrez, Ashraf Yusuf
M'Baya-Moutoula, Eléonore
Metzinger-Le Meuth, Valérie
Hénaut, Lucie
Djelouat, Mohamed Seif el Islam
Benchitrit, Joyce
Massy, Ziad A.
Metzinger, Laurent
Inorganic Phosphate Accelerates the Migration of Vascular Smooth Muscle Cells: Evidence for the Involvement of miR-223
title Inorganic Phosphate Accelerates the Migration of Vascular Smooth Muscle Cells: Evidence for the Involvement of miR-223
title_full Inorganic Phosphate Accelerates the Migration of Vascular Smooth Muscle Cells: Evidence for the Involvement of miR-223
title_fullStr Inorganic Phosphate Accelerates the Migration of Vascular Smooth Muscle Cells: Evidence for the Involvement of miR-223
title_full_unstemmed Inorganic Phosphate Accelerates the Migration of Vascular Smooth Muscle Cells: Evidence for the Involvement of miR-223
title_short Inorganic Phosphate Accelerates the Migration of Vascular Smooth Muscle Cells: Evidence for the Involvement of miR-223
title_sort inorganic phosphate accelerates the migration of vascular smooth muscle cells: evidence for the involvement of mir-223
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475714/
https://www.ncbi.nlm.nih.gov/pubmed/23094093
http://dx.doi.org/10.1371/journal.pone.0047807
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