Transcription factor ETS-1 and reactive oxygen species: Role in vascular and renal injury

Abstract

The E26 avian erythroblastosis virus transcription factor-1 (ETS-1) is a member of the ETS family and regulates the expression of a variety of genes including growth factors, chemokines and adhesion molecules. Although ETS-1 was discovered as an oncogene, several lines of research show that it is up-regulated by angiotensin II (Ang II) both in the vasculature and the glomerulus. While reactive oxygen species (ROS) are required for Ang II-induced ETS-1 expression, ETS-1 also regulates the expression of p47phox, which is one of the subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and a major source of ROS in the kidney and vasculature. Thus, there appears to be a positive feedback between ETS-1 and ROS. ETS-1 is also upregulated in the kidneys of rats with salt-sensitive hypertension and plays a major role in the development of end-organ injury in this animal model. Activation of the renin angiotensin system is required for the increased ETS-1 expression in these rats, and blockade of ETS-1 or haplodeficiency reduces the severity of kidney injury in these rats. In summary, ETS-1 plays a major role in the development of vascular and renal injury and is a potential target for the development of novel therapeutic strategies to ameliorate end-organ injury in hypertension.