Inhibition of microRNA-92a increases blood vessels and satellite cells in skeletal muscle but does not improve duchenne muscular dystrophy-related phenotype in mdx mice.

Inhibition of microRNA-92a increases blood vessels and satellite cells in skeletal muscle but does not improve duchenne muscular dystrophy-related phenotype in mdx mice.
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DOI:
10.1002/mus.26433
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发表时间:
2019-05
期刊:
影响因子:
3.4
通讯作者:
Asakura A
Asakura A
中科院分区:
医学3区
文献类型:
--
作者:
Verma M;Asakura Y;Asakura A

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Duchenne型肌营养不良症(DMD)及其mdx小鼠模型肌肉血管和血流受到干扰。microRNA-92 a(miR-92 a)在内皮细胞中富集,尤其是在缺血性损伤期间。由于拮抗miR-92 a显示出导致内皮细胞的增殖和迁移增加以及从缺血中恢复,因此我们评估了Antagomir-92 a在肌肉干细胞培养物中的体外作用和在mdx小鼠中的体内作用。发现miR-92 a在肌肉内皮细胞和卫星细胞中高度表达。用Antagomir-92 a处理增加毛细血管密度和组织灌注,这伴随着卫星细胞的增加。然而,Antagomir-92 a处理的mdx小鼠没有显示出组织学改善,并且具有更差的肌肉功能。Antagomir-92 a抑制卫星细胞培养中的成肌分化。AntagomiR-92 a改善了mdx小鼠的血管系统,但没有改善肌肉,这可能是由于其对卫星细胞分化的副作用。
The vasculature and blood flow in muscle are perturbed in Duchenne muscular dystrophy (DMD) and its mdx mouse model. MicroRNA-92a (miR-92a) is enriched in endothelial cells, especially during ischemic injury. Because antagonizing miR-92a was shown to result in increased proliferation and migration of endothelial cells and recovery from ischemia, we assessed the effects of Antagomir-92a in vitro in muscle stem cell culture and in vivo in mdx mice. miR-92a was found to be highly expressed in muscle endothelial cells and satellite cells. Treatment with Antagomir-92a increased capillary density and tissue perfusion, which was accompanied by an increase in satellite cells. However, Antagomir-92a–treated mdx mice showed no histological improvement and had worse muscle function. Antagomir-92a suppressed myogenic differentiation in satellite cell culture. AntagomiR-92a improves the vasculature but not the muscle in mdx mice, possibly due to its side effects on satellite cell differentiation.
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