Dihydroartemisinin inhibits the expression of von Willebrand factor by downregulation of transcription factor ERG in endothelial cells. (7th November 2020)

• Record Type: Journal Article
• Authors: Dong, Fengyun; Zhao, Xinghai; Wang, Jianning; Huang, Xin; Li, Xiao; Zhang, Liang; Dong, Haixin; Liu, Fuhong; Fan, Mengge
• Is Part Of: Fundamental & clinical pharmacology. Volume 35:Number 2(2021)
• Page Start: 321
• Page End: 330
• Publication Date: 2020-11-07
• Subjects: dihydroartemisinin -- ERG -- human umbilical vein endothelial cells -- von Willebrand Factor; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/fcp.12622
• Languages: English
• ISSNs: 0767-3981

Abstract

Abstract: Dihydroartemisinin (DHA), a semi‐synthetic derivative of artemisinin, has effective antitumor and anti‐inflammatory actions. von Willebrand factor (vWF), a large multifunctional glycoprotein, has a prominent function in hemostasis and is a key factor in thrombus formation. In addition, vWF has been regarded as a prospective biomarker for the diagnosis of endothelial dysfunction. In our experiment, we observed that 25 μM DHA specifically downregulated the expression of vWF mRNA and protein in human umbilical vein endothelial cells (HUVECs). Further investigations demonstrated that this DHA‐decreased vWF expression was mediated by the transcription factor ERG and not GATA3. Luciferase activity assay confirmed that DHA regulated the ERG binding with the −56 ETS‐binding motif on the human vWF promoter. Thus, the −56 ETS motif on the vWF promoter region regulates the expression of vWF gene which is induced by DHA. Taken together, we proved that DHA decreased the vWF transcription through the downregulation of ERG in HUVECs. As vWF plays a key role in vascular homeostasis, our findings suggest a new role of DHA in vascular diseases.