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Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation

DiGeorge syndrome chromosomal region 8 (DGCR8), a double-stranded-RNA-binding protein, participates in the miRNA biogenesis pathway and contributes to miRNA maturation by interacting with the RNAase III enzyme Drosha in cell nuclei. To investigate the role of DGCR8 in vascular smooth muscle cells (V...

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Autores principales: Zou, Yanan, Chen, Zixuan, Jennings, Brett L., Zhao, Guannan, Gu, Qingqing, Bhattacharya, Anindya, Cui, Yan, Yu, Bo, Malik, Kafait U., Yue, Junming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780492/
https://www.ncbi.nlm.nih.gov/pubmed/29362439
http://dx.doi.org/10.1038/s41598-018-19660-z
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author Zou, Yanan
Chen, Zixuan
Jennings, Brett L.
Zhao, Guannan
Gu, Qingqing
Bhattacharya, Anindya
Cui, Yan
Yu, Bo
Malik, Kafait U.
Yue, Junming
author_facet Zou, Yanan
Chen, Zixuan
Jennings, Brett L.
Zhao, Guannan
Gu, Qingqing
Bhattacharya, Anindya
Cui, Yan
Yu, Bo
Malik, Kafait U.
Yue, Junming
author_sort Zou, Yanan
collection PubMed
description DiGeorge syndrome chromosomal region 8 (DGCR8), a double-stranded-RNA-binding protein, participates in the miRNA biogenesis pathway and contributes to miRNA maturation by interacting with the RNAase III enzyme Drosha in cell nuclei. To investigate the role of DGCR8 in vascular smooth muscle cells (VSMCs) at the postnatal stages, we generated tamoxifen-inducible VSMC specific knockout (iKO) mice by crossing DGCR8(loxp/loxp) with VSMC specific tamoxifen-inducible Cre transgenic mice SMA-Cre-ER(T2). DGCR8iKO mice display reduced body weight one month following tamoxifen treatment and died around 3 months. Blood pressure and vascular reactivity were significantly reduced in DGCR8iKO mice compared to control. Furthermore, loss of DGCR8 in VSMCs inhibited cell proliferation, migration and neointima formation. VSMC differentiation marker genes, including SMA and SM22, were downregulated in DGCR8 iKO mice. The majority of miRNAs were downregulated in DGCR8iKO mice. Disruption of the DGCR8-mediated miRNA biogenesis pathway attenuated multiple signaling pathways including ERK1/2 and AKT. Our results demonstrate that the DGCR8-mediated miRNA pathway is required for maintaining blood pressure, vascular reactivity and vascular wall remodeling at the postnatal stages.
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spelling pubmed-57804922018-02-06 Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation Zou, Yanan Chen, Zixuan Jennings, Brett L. Zhao, Guannan Gu, Qingqing Bhattacharya, Anindya Cui, Yan Yu, Bo Malik, Kafait U. Yue, Junming Sci Rep Article DiGeorge syndrome chromosomal region 8 (DGCR8), a double-stranded-RNA-binding protein, participates in the miRNA biogenesis pathway and contributes to miRNA maturation by interacting with the RNAase III enzyme Drosha in cell nuclei. To investigate the role of DGCR8 in vascular smooth muscle cells (VSMCs) at the postnatal stages, we generated tamoxifen-inducible VSMC specific knockout (iKO) mice by crossing DGCR8(loxp/loxp) with VSMC specific tamoxifen-inducible Cre transgenic mice SMA-Cre-ER(T2). DGCR8iKO mice display reduced body weight one month following tamoxifen treatment and died around 3 months. Blood pressure and vascular reactivity were significantly reduced in DGCR8iKO mice compared to control. Furthermore, loss of DGCR8 in VSMCs inhibited cell proliferation, migration and neointima formation. VSMC differentiation marker genes, including SMA and SM22, were downregulated in DGCR8 iKO mice. The majority of miRNAs were downregulated in DGCR8iKO mice. Disruption of the DGCR8-mediated miRNA biogenesis pathway attenuated multiple signaling pathways including ERK1/2 and AKT. Our results demonstrate that the DGCR8-mediated miRNA pathway is required for maintaining blood pressure, vascular reactivity and vascular wall remodeling at the postnatal stages. Nature Publishing Group UK 2018-01-23 /pmc/articles/PMC5780492/ /pubmed/29362439 http://dx.doi.org/10.1038/s41598-018-19660-z Text en © The Author(s) 2018 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
Zou, Yanan
Chen, Zixuan
Jennings, Brett L.
Zhao, Guannan
Gu, Qingqing
Bhattacharya, Anindya
Cui, Yan
Yu, Bo
Malik, Kafait U.
Yue, Junming
Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation
title Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation
title_full Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation
title_fullStr Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation
title_full_unstemmed Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation
title_short Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation
title_sort deletion of dgcr8 in vsmcs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780492/
https://www.ncbi.nlm.nih.gov/pubmed/29362439
http://dx.doi.org/10.1038/s41598-018-19660-z
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