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MicroRNA-134-5p Regulates Media Degeneration through Inhibiting VSMC Phenotypic Switch and Migration in Thoracic Aortic Dissection

Abnormal phenotypic switch, migration, and proliferation of vascular smooth muscle cells (VSMCs) are hallmarks for pathogenesis of thoracic aortic dissection (TAD). In the current study, we identified miR-134-5p as a critical regulator controlling human VSMC phenotypic switch and migration to invest...

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Autores principales: Wang, Ying, Dong, Chang-Qing, Peng, Guang-Yin, Huang, Hao-yue, Yu, Yun-sheng, Ji, Zhen-Chun, Shen, Zhen-Ya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446055/
https://www.ncbi.nlm.nih.gov/pubmed/30951965
http://dx.doi.org/10.1016/j.omtn.2019.02.021
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author Wang, Ying
Dong, Chang-Qing
Peng, Guang-Yin
Huang, Hao-yue
Yu, Yun-sheng
Ji, Zhen-Chun
Shen, Zhen-Ya
author_facet Wang, Ying
Dong, Chang-Qing
Peng, Guang-Yin
Huang, Hao-yue
Yu, Yun-sheng
Ji, Zhen-Chun
Shen, Zhen-Ya
author_sort Wang, Ying
collection PubMed
description Abnormal phenotypic switch, migration, and proliferation of vascular smooth muscle cells (VSMCs) are hallmarks for pathogenesis of thoracic aortic dissection (TAD). In the current study, we identified miR-134-5p as a critical regulator controlling human VSMC phenotypic switch and migration to investigate whether miR-134-5p affects human VSMC functions and development of TAD. Using miRNA microarray of aorta specimens from 12 TAD and 12 controls, we identified miR-134-5p, which was significantly downregulated in TAD tissues. With qPCR detection, we found that miR-134-5p was also evidently decreased in human AoSMCs. Ectopic expression of miR-134-5p obviously promoted VSMC differentiation and expression of contractile markers, such as α-SMA, SM22α, and MYH11. miR-134-5p potently inhibited PDGF-BB-induced VSMC phenotypic switch and migration. We further identified STAT5B and ITGB1 as downstream targets of miR-134-5p in human VSMCs and proved them to be mediators in VSMC phenotypic switch and progression of TAD. Finally, Ad-miR-134-5p obviously suppressed the aorta dilatation and vascular media degeneration by 39% in TAD mice after vascular injury induced by Ang II. Our findings revealed that miR-134-5p was a novel regulator in vascular remodeling and pathological progress of TAD via targeting STAT5B/ITGB1 expression. Targeting miR-134-5p or its downstream molecules in VSMCs might develop new avenues in clinical treatment of TAD.
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spelling pubmed-64460552019-04-12 MicroRNA-134-5p Regulates Media Degeneration through Inhibiting VSMC Phenotypic Switch and Migration in Thoracic Aortic Dissection Wang, Ying Dong, Chang-Qing Peng, Guang-Yin Huang, Hao-yue Yu, Yun-sheng Ji, Zhen-Chun Shen, Zhen-Ya Mol Ther Nucleic Acids Article Abnormal phenotypic switch, migration, and proliferation of vascular smooth muscle cells (VSMCs) are hallmarks for pathogenesis of thoracic aortic dissection (TAD). In the current study, we identified miR-134-5p as a critical regulator controlling human VSMC phenotypic switch and migration to investigate whether miR-134-5p affects human VSMC functions and development of TAD. Using miRNA microarray of aorta specimens from 12 TAD and 12 controls, we identified miR-134-5p, which was significantly downregulated in TAD tissues. With qPCR detection, we found that miR-134-5p was also evidently decreased in human AoSMCs. Ectopic expression of miR-134-5p obviously promoted VSMC differentiation and expression of contractile markers, such as α-SMA, SM22α, and MYH11. miR-134-5p potently inhibited PDGF-BB-induced VSMC phenotypic switch and migration. We further identified STAT5B and ITGB1 as downstream targets of miR-134-5p in human VSMCs and proved them to be mediators in VSMC phenotypic switch and progression of TAD. Finally, Ad-miR-134-5p obviously suppressed the aorta dilatation and vascular media degeneration by 39% in TAD mice after vascular injury induced by Ang II. Our findings revealed that miR-134-5p was a novel regulator in vascular remodeling and pathological progress of TAD via targeting STAT5B/ITGB1 expression. Targeting miR-134-5p or its downstream molecules in VSMCs might develop new avenues in clinical treatment of TAD. American Society of Gene & Cell Therapy 2019-02-28 /pmc/articles/PMC6446055/ /pubmed/30951965 http://dx.doi.org/10.1016/j.omtn.2019.02.021 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Wang, Ying
Dong, Chang-Qing
Peng, Guang-Yin
Huang, Hao-yue
Yu, Yun-sheng
Ji, Zhen-Chun
Shen, Zhen-Ya
MicroRNA-134-5p Regulates Media Degeneration through Inhibiting VSMC Phenotypic Switch and Migration in Thoracic Aortic Dissection
title MicroRNA-134-5p Regulates Media Degeneration through Inhibiting VSMC Phenotypic Switch and Migration in Thoracic Aortic Dissection
title_full MicroRNA-134-5p Regulates Media Degeneration through Inhibiting VSMC Phenotypic Switch and Migration in Thoracic Aortic Dissection
title_fullStr MicroRNA-134-5p Regulates Media Degeneration through Inhibiting VSMC Phenotypic Switch and Migration in Thoracic Aortic Dissection
title_full_unstemmed MicroRNA-134-5p Regulates Media Degeneration through Inhibiting VSMC Phenotypic Switch and Migration in Thoracic Aortic Dissection
title_short MicroRNA-134-5p Regulates Media Degeneration through Inhibiting VSMC Phenotypic Switch and Migration in Thoracic Aortic Dissection
title_sort microrna-134-5p regulates media degeneration through inhibiting vsmc phenotypic switch and migration in thoracic aortic dissection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446055/
https://www.ncbi.nlm.nih.gov/pubmed/30951965
http://dx.doi.org/10.1016/j.omtn.2019.02.021
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