Low Dose Cadmium Upregulates the Expression of von Willebrand Factor in Endothelial Cells.

In this study, we observed that low dose Cd treatment induced von Willebrand factor (vWF) expression in vascular endothelial cells in mouse lung and kidney tissues. In vitro analysis showed that 1 μM Cd specifically upregulated vWF mRNA and protein expression in human umbilical vein endothelial cells (HUVECs), indicating that Cd targets vascular endothelial cells even at relatively low concentrations. Further study demonstrated that nuclear factor kappa B (NF-κB) and GATA3, two established transcription regulators of the vWF gene, were not altered in the presence of Cd. However, ETS-related gene (ERG) was significantly induced by 1 μM Cd. When ERG was knocked down by siRNA, Cd induced upregulation of vWF was totally blocked. Chromatin immunoprecipitation (ChIP) assay showed that Cd increases the binding of ERG on the -56 ETS motif on the human vWF promoter. These results indicated that ERG mediated the increased expression of vWF by Cd. Since vWF is a key regulator for vascular homeostasis, our findings may provide a novel mechanism for understanding low dose Cd induced development of vascular diseases. PMID: 29571895 [PubMed - as supplied by publisher]
Source: Toxicology Letters - Category: Toxicology Authors: Tags: Toxicol Lett Source Type: research