Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation.
Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity, reduced blood pressure and neointima formation.
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成年小鼠VSMC中DGCR8的缺失导致血管反应性丧失，血压降低和新内膜形成。
DOI：
10.1038/s41598-018-19660-z
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发表时间：
2018-01-23
影响因子：
4.6
通讯作者：
Yue J
中科院分区：
文献类型：
--
作者：
Zou Y;Chen Z;Jennings BL;Zhao G;Gu Q;Bhattacharya A;Cui Y;Yu B;Malik KU;Yue J
DiGeorge综合征染色体区8（DGCR 8）是一种双链RNA结合蛋白，参与miRNA生物合成途径，并通过与细胞核中的RNAase III酶Drosha相互作用促进miRNA成熟。为了研究DGCR 8在出生后阶段血管平滑肌细胞（VSMC）中的作用，我们通过将DGCR 8loxp/loxp与VSMC特异性他莫昔芬诱导的Cre转基因小鼠SMA-Cre-ERT 2杂交来产生他莫昔芬诱导的VSMC特异性敲除（iKO）小鼠。DGCR 8iKO小鼠在他莫昔芬治疗后一个月显示体重减轻，并在约3个月时死亡。与对照相比，DGCR 8iKO小鼠的血压和血管反应性显著降低。此外，VSMC中DGCR 8的缺失抑制细胞增殖、迁移和新生内膜形成。VSMC分化标记基因，包括SMA和SM 22，在DGCR 8 iKO小鼠中下调。大多数miRNA在DGCR 8iKO小鼠中下调。DGCR 8介导的miRNA生物合成途径的破坏减弱了包括ERK 1/2和AKT在内的多种信号传导途径。我们的研究结果表明，DGCR 8介导的miRNA途径是维持出生后阶段血压，血管反应性和血管壁重塑所必需的。
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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影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
DOI：
10.1093/bioinformatics/bts251
发表时间：
2012-07-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Jiao X;Sherman BT;Huang da W;Stephens R;Baseler MW;Lane HC;Lempicki RA
通讯作者：
Lempicki RA
影响因子：
4.8
作者：
Chen, Zixuan;Wu, Jianmin;Yue, Junming
通讯作者：
Yue, Junming
影响因子：
9.2
作者：
Landthaler, M;Yalcin, A;Tuschl, T
通讯作者：
Tuschl, T
DOI：
10.1126/science.1190809
发表时间：
2010-06-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cifuentes D;Xue H;Taylor DW;Patnode H;Mishima Y;Cheloufi S;Ma E;Mane S;Hannon GJ;Lawson ND;Wolfe SA;Giraldez AJ
通讯作者：
Giraldez AJ