Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, United States.
Biochem Biophys Res Commun. 2011 May 13;408(3):369-74. doi: 10.1016/j.bbrc.2011.02.119. Epub 2011 Feb 28.
Dicer is a RNAase III enzyme that cleaves double stranded RNA and generates small interfering RNA (siRNA) and microRNA (miRNA). The goal of this study is to examine the role of Dicer and miRNAs in vascular smooth muscle cells (VSMCs). We deleted Dicer in VSMCs of mice, which caused a developmental delay that manifested as early as embryonic day E12.5, leading to embryonic death between E14.5 and E15.5 due to extensive hemorrhage in the liver, brain, and skin. Dicer KO embryos showed dilated blood vessels and a disarray of vascular architecture between E14.5 and E15.5. VSMC proliferation was significantly inhibited in Dicer KOs. The expression of VSMC marker genes were significantly downregulated in Dicer cKO embryos. The vascular structure of the yolk sac and embryo in Dicer KOs was lost to an extent that no blood vessels could be identified after E15.5. Expression of most miRNAs examined was compromised in VSMCs of Dicer KO. Our results indicate that Dicer is required for vascular development and regulates vascular remodeling by modulating VSMC proliferation and differentiation.
Dicer 是一种 RNAase III 酶,可切割双链 RNA,并生成小干扰 RNA(siRNA)和 microRNA(miRNA)。本研究的目的是研究 Dicer 和 miRNAs 在血管平滑肌细胞(VSMCs)中的作用。我们在小鼠的 VSMCs 中敲除了 Dicer,这导致了发育迟缓,早在胚胎第 12.5 天(E12.5)就表现出来,由于肝脏、大脑和皮肤广泛出血,导致胚胎在 E14.5 至 E15.5 之间死亡。Dicer KO 胚胎显示出血管扩张和血管结构紊乱,E14.5 至 E15.5 之间。Dicer KOs 中 VSMC 增殖受到显著抑制。Dicer cKO 胚胎中 VSMC 标记基因的表达显著下调。Dicer KO 中的卵黄囊和胚胎的血管结构丢失到一定程度,以至于在 E15.5 之后无法识别任何血管。Dicer KO 的 VSMCs 中大多数检查的 miRNAs 的表达受到损害。我们的结果表明,Dicer 是血管发育所必需的,通过调节 VSMC 增殖和分化来调节血管重塑。
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