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

Abstract 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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yanan Zou, Zixuan Chen, Brett L. Jennings, Guannan Zhao, Qingqing Gu, Anindya Bhattacharya, Yan Cui, Bo Yu, Kafait U. Malik, Junming Yue
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/90feae036d2142ddaee68bc5e079a4f0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:90feae036d2142ddaee68bc5e079a4f0
record_format	dspace
spelling	oai:doaj.org-article:90feae036d2142ddaee68bc5e079a4f02021-12-02T15:07:46ZDeletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation10.1038/s41598-018-19660-z2045-2322https://doaj.org/article/90feae036d2142ddaee68bc5e079a4f02018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19660-zhttps://doaj.org/toc/2045-2322Abstract 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 DGCR8loxp/loxp with VSMC specific tamoxifen-inducible Cre transgenic mice SMA-Cre-ERT2. 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.Yanan ZouZixuan ChenBrett L. JenningsGuannan ZhaoQingqing GuAnindya BhattacharyaYan CuiBo YuKafait U. MalikJunming YueNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yanan Zou Zixuan Chen Brett L. Jennings Guannan Zhao Qingqing Gu Anindya Bhattacharya Yan Cui Bo Yu Kafait U. Malik Junming Yue Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation
description	Abstract 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 DGCR8loxp/loxp with VSMC specific tamoxifen-inducible Cre transgenic mice SMA-Cre-ERT2. 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.
format	article
author	Yanan Zou Zixuan Chen Brett L. Jennings Guannan Zhao Qingqing Gu Anindya Bhattacharya Yan Cui Bo Yu Kafait U. Malik Junming Yue
author_facet	Yanan Zou Zixuan Chen Brett L. Jennings Guannan Zhao Qingqing Gu Anindya Bhattacharya Yan Cui Bo Yu Kafait U. Malik Junming Yue
author_sort	Yanan Zou
title	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_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_sort	deletion of dgcr8 in vsmcs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/90feae036d2142ddaee68bc5e079a4f0
work_keys_str_mv	AT yananzou deletionofdgcr8invsmcsofadultmiceresultsinlossofvascularreactivityreducedbloodpressureandneointimaformation AT zixuanchen deletionofdgcr8invsmcsofadultmiceresultsinlossofvascularreactivityreducedbloodpressureandneointimaformation AT brettljennings deletionofdgcr8invsmcsofadultmiceresultsinlossofvascularreactivityreducedbloodpressureandneointimaformation AT guannanzhao deletionofdgcr8invsmcsofadultmiceresultsinlossofvascularreactivityreducedbloodpressureandneointimaformation AT qingqinggu deletionofdgcr8invsmcsofadultmiceresultsinlossofvascularreactivityreducedbloodpressureandneointimaformation AT anindyabhattacharya deletionofdgcr8invsmcsofadultmiceresultsinlossofvascularreactivityreducedbloodpressureandneointimaformation AT yancui deletionofdgcr8invsmcsofadultmiceresultsinlossofvascularreactivityreducedbloodpressureandneointimaformation AT boyu deletionofdgcr8invsmcsofadultmiceresultsinlossofvascularreactivityreducedbloodpressureandneointimaformation AT kafaitumalik deletionofdgcr8invsmcsofadultmiceresultsinlossofvascularreactivityreducedbloodpressureandneointimaformation AT junmingyue deletionofdgcr8invsmcsofadultmiceresultsinlossofvascularreactivityreducedbloodpressureandneointimaformation
_version_	1718388403436781568

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

Ejemplares similares