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miR-18a-5p MicroRNA Increases Vascular Smooth Muscle Cell Differentiation by Downregulating Syndecan4

BACKGROUND AND OBJECTIVES: Differentiation and de-differentiation of vascular smooth muscle cells (VSMCs) are important events in atherosclerosis and restenosis after angioplasty. MicroRNAs are considered a key regulator in cellular processes such as differentiation, proliferation, and apoptosis. He...

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Autores principales: Kee, Hae Jin, Kim, Gwi Ran, Cho, Soo-Na, Kwon, Jin-Sook, Ahn, Youngkeun, Kook, Hyun, Jeong, Myung Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Cardiology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117847/
https://www.ncbi.nlm.nih.gov/pubmed/25089138
http://dx.doi.org/10.4070/kcj.2014.44.4.255
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author Kee, Hae Jin
Kim, Gwi Ran
Cho, Soo-Na
Kwon, Jin-Sook
Ahn, Youngkeun
Kook, Hyun
Jeong, Myung Ho
author_facet Kee, Hae Jin
Kim, Gwi Ran
Cho, Soo-Na
Kwon, Jin-Sook
Ahn, Youngkeun
Kook, Hyun
Jeong, Myung Ho
author_sort Kee, Hae Jin
collection PubMed
description BACKGROUND AND OBJECTIVES: Differentiation and de-differentiation of vascular smooth muscle cells (VSMCs) are important events in atherosclerosis and restenosis after angioplasty. MicroRNAs are considered a key regulator in cellular processes such as differentiation, proliferation, and apoptosis. Here, we report the role of new miR-18a-5p microRNA and its downstream target genes in VSMCs and in a carotid balloon injury model. MATERIALS AND METHODS: Expression of miR-18a-5p and its candidate genes was examined in VSMCs and in a carotid artery injury model by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and microRNA microarray analysis. VSMC differentiation marker genes including smooth muscle (SM) α-actin and SM22α were determined by Western blot, qRT-PCR, and a SM22α promoter study. Gene overexpression or knockdown was performed in VSMCs. RESULTS: miR-18a-5p was upregulated in the rat carotid artery at the early time after balloon injury. Transfection of the miR-18a-5p mimic promoted the VSMC differentiation markers SM α-actin and SM22α. In addition, miR-18a-5p expression was induced in differentiated VSMCs, whereas it decreased in de-differentiated VSMCs. We identified syndecan4 as a downstream target of miR-18-5p in VSMCs. Overexpression of syndecan4 decreased Smad2 expression, whereas knockdown of syndecan4 increased Smad2 expression in VSMCs. Finally, we showed that Smad2 induced the expression of VSMC differentiation marker genes in VSMCs. CONCLUSION: These results indicate that miR-18a-5p is involved in VSMC differentiation by targeting syndecan4.
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spelling pubmed-41178472014-08-01 miR-18a-5p MicroRNA Increases Vascular Smooth Muscle Cell Differentiation by Downregulating Syndecan4 Kee, Hae Jin Kim, Gwi Ran Cho, Soo-Na Kwon, Jin-Sook Ahn, Youngkeun Kook, Hyun Jeong, Myung Ho Korean Circ J Original Article BACKGROUND AND OBJECTIVES: Differentiation and de-differentiation of vascular smooth muscle cells (VSMCs) are important events in atherosclerosis and restenosis after angioplasty. MicroRNAs are considered a key regulator in cellular processes such as differentiation, proliferation, and apoptosis. Here, we report the role of new miR-18a-5p microRNA and its downstream target genes in VSMCs and in a carotid balloon injury model. MATERIALS AND METHODS: Expression of miR-18a-5p and its candidate genes was examined in VSMCs and in a carotid artery injury model by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and microRNA microarray analysis. VSMC differentiation marker genes including smooth muscle (SM) α-actin and SM22α were determined by Western blot, qRT-PCR, and a SM22α promoter study. Gene overexpression or knockdown was performed in VSMCs. RESULTS: miR-18a-5p was upregulated in the rat carotid artery at the early time after balloon injury. Transfection of the miR-18a-5p mimic promoted the VSMC differentiation markers SM α-actin and SM22α. In addition, miR-18a-5p expression was induced in differentiated VSMCs, whereas it decreased in de-differentiated VSMCs. We identified syndecan4 as a downstream target of miR-18-5p in VSMCs. Overexpression of syndecan4 decreased Smad2 expression, whereas knockdown of syndecan4 increased Smad2 expression in VSMCs. Finally, we showed that Smad2 induced the expression of VSMC differentiation marker genes in VSMCs. CONCLUSION: These results indicate that miR-18a-5p is involved in VSMC differentiation by targeting syndecan4. The Korean Society of Cardiology 2014-07 2014-07-25 /pmc/articles/PMC4117847/ /pubmed/25089138 http://dx.doi.org/10.4070/kcj.2014.44.4.255 Text en Copyright © 2014 The Korean Society of Cardiology http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Kee, Hae Jin
Kim, Gwi Ran
Cho, Soo-Na
Kwon, Jin-Sook
Ahn, Youngkeun
Kook, Hyun
Jeong, Myung Ho
miR-18a-5p MicroRNA Increases Vascular Smooth Muscle Cell Differentiation by Downregulating Syndecan4
title miR-18a-5p MicroRNA Increases Vascular Smooth Muscle Cell Differentiation by Downregulating Syndecan4
title_full miR-18a-5p MicroRNA Increases Vascular Smooth Muscle Cell Differentiation by Downregulating Syndecan4
title_fullStr miR-18a-5p MicroRNA Increases Vascular Smooth Muscle Cell Differentiation by Downregulating Syndecan4
title_full_unstemmed miR-18a-5p MicroRNA Increases Vascular Smooth Muscle Cell Differentiation by Downregulating Syndecan4
title_short miR-18a-5p MicroRNA Increases Vascular Smooth Muscle Cell Differentiation by Downregulating Syndecan4
title_sort mir-18a-5p microrna increases vascular smooth muscle cell differentiation by downregulating syndecan4
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117847/
https://www.ncbi.nlm.nih.gov/pubmed/25089138
http://dx.doi.org/10.4070/kcj.2014.44.4.255
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