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Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification

Vascular calcification is characterized by the accumulation of hydroxyapatite crystals, which is a result of aberrant mineral metabolism. Although many clinical studies have reported its adverse effects on cardiovascular morbidity, the molecular mechanism of vascular calcification, especially the in...

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Autores principales: Jeong, Geon, Kwon, Duk-Hwa, Shin, Sera, Choe, Nakwon, Ryu, Juhee, Lim, Yeong-Hwan, Kim, Jaetaek, Park, Woo Jin, Kook, Hyun, Kim, Young-Kook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458154/
https://www.ncbi.nlm.nih.gov/pubmed/30971745
http://dx.doi.org/10.1038/s41598-019-42283-x
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author Jeong, Geon
Kwon, Duk-Hwa
Shin, Sera
Choe, Nakwon
Ryu, Juhee
Lim, Yeong-Hwan
Kim, Jaetaek
Park, Woo Jin
Kook, Hyun
Kim, Young-Kook
author_facet Jeong, Geon
Kwon, Duk-Hwa
Shin, Sera
Choe, Nakwon
Ryu, Juhee
Lim, Yeong-Hwan
Kim, Jaetaek
Park, Woo Jin
Kook, Hyun
Kim, Young-Kook
author_sort Jeong, Geon
collection PubMed
description Vascular calcification is characterized by the accumulation of hydroxyapatite crystals, which is a result of aberrant mineral metabolism. Although many clinical studies have reported its adverse effects on cardiovascular morbidity, the molecular mechanism of vascular calcification, especially the involvement of long noncoding RNAs (lncRNAs), is not yet reported. From the transcriptomic analysis, we discovered hundreds of lncRNAs differentially expressed in rat vascular smooth muscle cells (VSMCs) treated with inorganic phosphate, which mimics vascular calcification. We focused on Lrrc75a-as1 and elucidated its transcript structure and confirmed its cytoplasmic localization. Our results showed that calcium deposition was elevated after knockdown of Lrrc75a-as1, while its overexpression inhibited calcium accumulation in A10 cells. In addition, Lrrc75a-as1 attenuated VSMCs calcification by decreasing the expression of osteoblast-related factors. These findings suggest that Lrrc75a-as1 acts as a negative regulator of vascular calcification, and may serve as a possible therapeutic target in vascular calcification.
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spelling pubmed-64581542019-04-15 Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification Jeong, Geon Kwon, Duk-Hwa Shin, Sera Choe, Nakwon Ryu, Juhee Lim, Yeong-Hwan Kim, Jaetaek Park, Woo Jin Kook, Hyun Kim, Young-Kook Sci Rep Article Vascular calcification is characterized by the accumulation of hydroxyapatite crystals, which is a result of aberrant mineral metabolism. Although many clinical studies have reported its adverse effects on cardiovascular morbidity, the molecular mechanism of vascular calcification, especially the involvement of long noncoding RNAs (lncRNAs), is not yet reported. From the transcriptomic analysis, we discovered hundreds of lncRNAs differentially expressed in rat vascular smooth muscle cells (VSMCs) treated with inorganic phosphate, which mimics vascular calcification. We focused on Lrrc75a-as1 and elucidated its transcript structure and confirmed its cytoplasmic localization. Our results showed that calcium deposition was elevated after knockdown of Lrrc75a-as1, while its overexpression inhibited calcium accumulation in A10 cells. In addition, Lrrc75a-as1 attenuated VSMCs calcification by decreasing the expression of osteoblast-related factors. These findings suggest that Lrrc75a-as1 acts as a negative regulator of vascular calcification, and may serve as a possible therapeutic target in vascular calcification. Nature Publishing Group UK 2019-04-10 /pmc/articles/PMC6458154/ /pubmed/30971745 http://dx.doi.org/10.1038/s41598-019-42283-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jeong, Geon
Kwon, Duk-Hwa
Shin, Sera
Choe, Nakwon
Ryu, Juhee
Lim, Yeong-Hwan
Kim, Jaetaek
Park, Woo Jin
Kook, Hyun
Kim, Young-Kook
Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification
title Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification
title_full Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification
title_fullStr Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification
title_full_unstemmed Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification
title_short Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification
title_sort long noncoding rnas in vascular smooth muscle cells regulate vascular calcification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458154/
https://www.ncbi.nlm.nih.gov/pubmed/30971745
http://dx.doi.org/10.1038/s41598-019-42283-x
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