Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
RNA Sequencing Reveals the Activation of Wnt Signaling in Low Flow Rate Brain Arteriovenous Malformations
First author：Huo Ran,Fu Weilun
Corresponding author：Cao Yong
essential_information
- Person in charge：Huo Ran,Fu Weilun
- Data Sources： OTHERS
- Number of papers：OTHERS20190790
- Published time：2019-06-18
2019-06-18
Published articles
Journal：Journal of the American Heart Association
Publication type: Original Research
IF(IF): 5.501
PMID: 31170876 Link To Pubmed Full text Download
Background And Purpose
Method
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.
Conclusion
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.
Main results
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.