Dihydroartemisinin inhibits the expression of von Willebrand factor by downregulation of transcription factor ERG in endothelial cells

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.

Dexmedetomidine attenuates renal ischemia–reperfusion injury through activating PI3K/Akt‐eNOS signaling via α2 adrenoreceptors in renal microvascular endothelial cells

“…The neonatal mouse kidney tissues was chosen to isolate RMECs in our current study considering that some previous reports demonstrated the isolation of endothelial cells from neonatal mice kidney tissues that can be reliably cultured to at least passage eight, enable a more complete digestion of the tissue and dispersal of the cells, produce more viable cells after sorting, and minimize fibroblast contamination, but the application of the procedures to isolate endothelial cells from older or adult mice results in cultures that are more susceptible to fibroblast overgrowth and the isolation of ECs that rapidly become senescent 21,22 . The vWF mainly produced by endothelial cells was regarded as a promising biomarker for endothelial dysfunction 23 . Thus, the purity of RMECs harvested from the kidney tissue in neonatal mice was identified by the immunofluorescence staining with vWF (Figure 6C).…”

“…21,22 The vWF mainly produced by endothelial cells was regarded as a promising biomarker for endothelial dysfunction. 23 Thus, the purity of RMECs harvested from the kidney tissue in neonatal mice was identified by the immunofluorescence staining with vWF (Figure 6C). And our results showed that the purity of cultured RMECs was 92.42% (Figure 6D).…”

Computer simulation and prediction of spectral and molecular properties of artemisinin

“…Artemisinin and its derivatives are active against not only plasmodium but also schistosome, pathogens and insects [4][5][6][7] . Furthermore, artemisinin and its derivatives have strong antitumor, anti-inflammatory and antidiabetic effects [8][9][10][11] . Though the exact antimalarial mechanism remains largely controversial, it is generally assumed that the endoperoxide bridge of artemisinin is the main mechanism of antimalarial action [12] .…”