国家神经系统疾病临床医学研究中心数据管理与共享系统

Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases

《国家中心数据管理与共享系统操作说明书 —— 研究者部分》

RNA Sequencing Reveals the Activation of Wnt Signaling in Low Flow Rate Brain Arteriovenous Malformations

第一作者：Huo Ran,Fu Weilun

通讯作者：Cao Yong

intracranial arteriovenous malformations gene expr

基本信息

2019-06-18

已发表文章

发表杂志：Journal of the American Heart Association

发表类型: Original Research

影响因子(IF): 5.501

PMID: 31170876 Pubmed原文链接 全文下载

主要研究背景及目的

方法

To identify potential key molecules, signaling pathways, and vascular cell types involved, we compared gene expression profiles between bAVM s with high flow rates and low flow rates ( LFR ) and validated the functions of selected key molecules in vitro.

结论

Our results suggest that canonical Wnt signaling mediated by FZD 10 and MYOC is activated in vascular endothelial and smooth muscle cells in LFR bAVM s.

主要结果

We performed RNA -sequencing analysis on 51 samples, including 14 high flow rate bAVM s and 37 LFR bAVM s. Functional pathway analysis was performed to identify potential signals influencing the flow rate phenotype of bAVM s. Candidate genes were investigated in bAVM specimens by immunohistochemical staining. Migration, tube formation, and proliferation assays were used to test the effects of candidate genes on the phenotypic properties of cultured human umbilical vein endothelial cells and human brain vascular smooth muscle cells. We identified 250 upregulated and 118 downregulated genes in LFR bAVM s compared with high flow rate bAVM s. Wnt signaling was activated in the LFR group via upregulation of FZD 10 and MYOC . Immunohistochemical staining showed that vascular endothelial and smooth muscle cells of LFR bAVM s exhibited increased FZD 10 and MYOC expression. Experimentally elevating these genes promoted human umbilical vein endothelial cells and migration and tube formation by activating canonical Wnt signaling in vitro.