MicroRNA-449c-5p inhibits osteogenic differentiation of human VICs through Smad4-mediated pathway

Abstract Calcific aortic valve disease (CAVD) is the most common heart valve disorder, yet its mechanism remains poorly understood. Valve interstitial cells (VICs) are the prevalent cells in aortic valve and their osteogenic differentiation may be responsible for calcific nodule formation in CAVD pa...

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Autores principales:	Rongjian Xu, Min Zhao, Yun Yang, Zhuo Huang, Chunying Shi, Xianglin Hou, Yannan Zhao, Bing Chen, Zhifeng Xiao, Jianzhou Liu, Qi Miao, Jianwu Dai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d1162d7bcc4b49c592bdfd9f316410a6
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spelling	oai:doaj.org-article:d1162d7bcc4b49c592bdfd9f316410a62021-12-02T16:06:08ZMicroRNA-449c-5p inhibits osteogenic differentiation of human VICs through Smad4-mediated pathway10.1038/s41598-017-09390-z2045-2322https://doaj.org/article/d1162d7bcc4b49c592bdfd9f316410a62017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09390-zhttps://doaj.org/toc/2045-2322Abstract Calcific aortic valve disease (CAVD) is the most common heart valve disorder, yet its mechanism remains poorly understood. Valve interstitial cells (VICs) are the prevalent cells in aortic valve and their osteogenic differentiation may be responsible for calcific nodule formation in CAVD pathogenesis. Emerging evidence shows microRNA (miRNA, or miR) can function as important regulators of many pathological processes, including osteogenic differentiation. Here, we aimed to explore the function of miR-449c-5p in CAVD pathogenesis. In this study, we demonstrated the role of miR-449c-5p in VICs osteogenesis. MiRNA microarray assay and qRT-PCR results revealed miR-449c-5p was significantly down-regulated in calcified aortic valves compared with non-calcified valves. MiR-449c-5p overexpression inhibited VICs osteogenic differentiation in vitro, whereas down-regulation of miR-449c-5p enhanced the process. Target prediction analysis and dual-luciferase reporter assay confirmed Smad4 was a direct target of miR-449c-5p. Furthermore, knockdown of Smad4 inhibited VICs osteogenic differentiation, similar to the effect observed in up-regulation miR-449c-5p. In addition, animal experiments proved indirectly miR-449c-5p could alleviate aortic valve calcification. Our data suggested miR-449c-5p could function as a new inhibitory regulator of VICs osteogenic differentiation, which may act by targeting Smad4. MiR-449c-5p may be a potential therapeutic target for CAVD.Rongjian XuMin ZhaoYun YangZhuo HuangChunying ShiXianglin HouYannan ZhaoBing ChenZhifeng XiaoJianzhou LiuQi MiaoJianwu DaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rongjian Xu Min Zhao Yun Yang Zhuo Huang Chunying Shi Xianglin Hou Yannan Zhao Bing Chen Zhifeng Xiao Jianzhou Liu Qi Miao Jianwu Dai MicroRNA-449c-5p inhibits osteogenic differentiation of human VICs through Smad4-mediated pathway
description	Abstract Calcific aortic valve disease (CAVD) is the most common heart valve disorder, yet its mechanism remains poorly understood. Valve interstitial cells (VICs) are the prevalent cells in aortic valve and their osteogenic differentiation may be responsible for calcific nodule formation in CAVD pathogenesis. Emerging evidence shows microRNA (miRNA, or miR) can function as important regulators of many pathological processes, including osteogenic differentiation. Here, we aimed to explore the function of miR-449c-5p in CAVD pathogenesis. In this study, we demonstrated the role of miR-449c-5p in VICs osteogenesis. MiRNA microarray assay and qRT-PCR results revealed miR-449c-5p was significantly down-regulated in calcified aortic valves compared with non-calcified valves. MiR-449c-5p overexpression inhibited VICs osteogenic differentiation in vitro, whereas down-regulation of miR-449c-5p enhanced the process. Target prediction analysis and dual-luciferase reporter assay confirmed Smad4 was a direct target of miR-449c-5p. Furthermore, knockdown of Smad4 inhibited VICs osteogenic differentiation, similar to the effect observed in up-regulation miR-449c-5p. In addition, animal experiments proved indirectly miR-449c-5p could alleviate aortic valve calcification. Our data suggested miR-449c-5p could function as a new inhibitory regulator of VICs osteogenic differentiation, which may act by targeting Smad4. MiR-449c-5p may be a potential therapeutic target for CAVD.
format	article
author	Rongjian Xu Min Zhao Yun Yang Zhuo Huang Chunying Shi Xianglin Hou Yannan Zhao Bing Chen Zhifeng Xiao Jianzhou Liu Qi Miao Jianwu Dai
author_facet	Rongjian Xu Min Zhao Yun Yang Zhuo Huang Chunying Shi Xianglin Hou Yannan Zhao Bing Chen Zhifeng Xiao Jianzhou Liu Qi Miao Jianwu Dai
author_sort	Rongjian Xu
title	MicroRNA-449c-5p inhibits osteogenic differentiation of human VICs through Smad4-mediated pathway
title_short	MicroRNA-449c-5p inhibits osteogenic differentiation of human VICs through Smad4-mediated pathway
title_full	MicroRNA-449c-5p inhibits osteogenic differentiation of human VICs through Smad4-mediated pathway
title_fullStr	MicroRNA-449c-5p inhibits osteogenic differentiation of human VICs through Smad4-mediated pathway
title_full_unstemmed	MicroRNA-449c-5p inhibits osteogenic differentiation of human VICs through Smad4-mediated pathway
title_sort	microrna-449c-5p inhibits osteogenic differentiation of human vics through smad4-mediated pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d1162d7bcc4b49c592bdfd9f316410a6
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MicroRNA-449c-5p inhibits osteogenic differentiation of human VICs through Smad4-mediated pathway

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