WD Repeat Domain 1 Deficiency Inhibits Neointima Formation in Mice Carotid Artery by Modulation of Smooth Muscle Cell Migration and Proliferation
WD Repeat Domain 1 Deficiency Inhibits Neointima Formation in Mice Carotid Artery by Modulation of Smooth Muscle Cell Migration and Proliferation
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WD 重复结构域 1 缺陷通过调节平滑肌细胞迁移和增殖抑制小鼠颈动脉新内膜形成
DOI：
10.14348/molcells.2020.0085
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发表时间：
2020-08-01
影响因子：
3.8
通讯作者：
Yuan, BaiYin
中科院分区：
文献类型：
--
作者：
Hu, JiSheng;Pi, ShangJing;Yuan, BaiYin
血管平滑肌细胞(VSMCs)的迁移、去分化和增殖与内膜增生有关，但这一过程的机制尚未阐明。WD重复结构域1(WDR1)促进肌动蛋白解聚因子(ADF)/辅丝蛋白介导的肌动蛋白细丝解聚(F-肌动蛋白)。WDR1在新生内膜形成和发展中的作用尚不清楚。结扎Wdr1基因缺失小鼠左侧颈总动脉建立血管内膜增厚模型，H&E染色显示Wdr1基因缺失可显著抑制新生内膜的形成。我们还报道，STAT3通过直接促进WDR1转录来促进VSMCs的增殖和迁移。我们从机制上阐明了WDR1促进VSMCs的增殖和迁移，而新生内膜的形成是通过激活JAK2/STAT3/WDR1轴来调节的。
The migration, dedifferentiation, and proliferation of vascular smooth muscle cells (VSMCs) are responsible for intimal hyperplasia, but the mechanism of this process has not been elucidated. WD repeat domain 1 (WDR1) promotes actin-depolymerizing factor (ADF)/cofilin-mediated depolymerization of actin filaments (F-actin). The role of WDR1 in neointima formation and progression is still unknown. A model of intimal thickening was constructed by ligating the left common carotid artery in Wdr1 deletion mice, and H&E staining showed that Wdr1 deficiency significantly inhibits neointima formation. We also report that STAT3 promotes the proliferation and migration of VSMCs by directly promoting WDR1 transcription. Mechanistically, we clarified that WDR1 promotes the proliferation and migration of VSMCs and neointima formation is regulated by the activation of the JAK2/STAT3/WDR1 axis.