The inhibition of the effect and mechanism of vascular intimal hyperplasia in Tiam1 knockout mice
The inhibition of the effect and mechanism of vascular intimal hyperplasia in Tiam1 knockout mice
复制标题
Tiam1基因敲除小鼠血管内膜增生的抑制作用及机制
DOI：
10.1016/j.bbrc.2018.02.065
复制
发表时间：
2018
影响因子：
3.1
通讯作者：
Peng Wenhui
中科院分区：
文献类型：
--
作者：
Kou Wenxin;Xu Xu;Ji Shuya;Chen Mengyao;Liu Dongdong;Wang Kai;Zhuang Jianhui;Yu Qing;Zhao Qian;Xu Yawei;Zhang Hongli;Peng Wenhui
T-Cell Lymphoma Invasion and Metastasis 1（Tiam 1）是一种特异性的核苷酸交换因子（GEF），可激活Rho样GT3和Rac 1，调节细胞周期进程和细胞迁移等多种细胞过程。Tiam 1在血管内膜增生，特别是血管平滑肌细胞增殖和迁移中的作用尚未完全了解。在这项研究中，我们研究了Tiam 1对颈动脉结扎模型和人主动脉平滑肌细胞（HASMCs）中血管内膜增生的影响。我们发现Tiam 1的表达在颈动脉结扎小鼠的新生内膜中上调，并且与野生型小鼠相比，颈动脉结扎后的Tiam 1 −/−小鼠的新生内膜形成较少。siRNA敲低Tiam 1可通过抑制Rac 1的活化，显著减弱PDGF诱导的HASMCs迁移和增殖。因此，这些结果表明Tiam 1是内膜增生的重要调节因子。它可能通过激活Rac 1调节血管内膜增生。
T-Cell Lymphoma Invasion and Metastasis 1 (Tiam1) is a specific nucleotide exchange factor (GEF) that can activate Rho-like GTPase and Rac1 and regulate various cellular processes, including cell cycle progression and cell migration. The roles of Tiam1 in vascular intimal hyperplasia, especially in vascular smooth muscle cell proliferation and migration, are not fully understood. In this study, we investigated the effect of Tiam1 on vascular intimal hyperplasia in a carotid artery ligation model and human aortic smooth muscle cells (HASMCs). We found that the expression of Tiam1 was up-regulated in the neointima of carotid artery ligation mice and that Tiam1−/−mice following carotid artery ligation had less neointimal formation compared with wild type mice. Knockdown of Tiam1 by siRNA markedly attenuated PDGF-induced migration and proliferation in HASMCs by inhibiting the activation of Rac1. Therefore, these results suggest that Tiam1 is an important regulator of intima hyperplasia. It may regulate vascular intimal hyperplasia through the activation of Rac1.