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

2019-03-02T15:52:03Z (GMT) by Junming Yue
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.

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