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Sci Rep. 2018 Jan 23;8(1):1468. doi: 10.1038/s41598-018-19660-z.

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

Author information

1
Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, P.R. China.
2
Departments of Pathology, The University of Tennessee Health Science Center, 19 S. Manassas St., Memphis, TN, 38163, USA.
3
School of Life Science, Beijing Institute of Technology, Beijing, P.R. China.
4
Departments of Pharmacology, The University of Tennessee Health Science Center, 19 S. Manassas St., Memphis, TN, 38163, USA.
5
Department of Genetics Genomics and Informatics, The University of Tennessee Health Science Center, 19 S. Manassas St., Memphis, TN, 38163, USA.
6
Departments of Pharmacology, The University of Tennessee Health Science Center, 19 S. Manassas St., Memphis, TN, 38163, USA. kmalik@uthsc.edu.
7
Departments of Pathology, The University of Tennessee Health Science Center, 19 S. Manassas St., Memphis, TN, 38163, USA. jyue@uthsc.edu.

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.

PMID:
29362439
PMCID:
PMC5780492
DOI:
10.1038/s41598-018-19660-z
[Indexed for MEDLINE]
Free PMC Article

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