ETS1 (Phospho-Thr38) ELISA Kit

Mutations in and reduced expression of the ETS1 gene may be associated with systemic lupus erythematosus (SLE). Here, we report a replication study to investigate associations of eight ETS1 single-nucleotide polymorphisms in the 3'-untranslated region (3'-UTR) with SLE and their regulation of ETS1 expression in a study population. We found that the rs4937333 T allele was associated with a significantly increased risk of SLE (odds ratio: 1.800, 95% confidence interval: 1.02-3.157, P = 0.040) and with dramatically reduced levels of ETS1 in B cells from SLE subjects. Functionally, the rs4937333 T allele alters the binding affinity between miR-5003 and its ETS1 3'-UTR target, thus enhancing suppression of ETS1 expression. Furthermore, immunoglobulin M-secreting plasmacytes were significantly reduced among B cells with the rs4937333 C allele versus the T allele according to FACS and ELISA. Additionally, miR-5003 expression was higher in B cells than in T cells from SLE patients, and a negative correlation between miR-5003 and ETS1 was found, especially in B cells with the T allele. These findings suggest that the rs4937333 T allele is a risk factor for susceptibility to SLE in the studied population. The rs4937333 T allele may enhance the binding of miR-5003 to ETS1, which probably promotes the involvement of ETS1 in the differentiation of B cells into plasmacytes.

Prior studies reported that haploinsufficiency of the transcription factor ETS-1 is renoprotective in Dahl salt-sensitive rats, but the mechanism is unclear. Here, we tested whether ETS-1 is involved in hypertension-induced renal microvascular pathology and autoregulatory impairment. Hypertension was induced in salt-sensitive rats and salt-sensitive rats that are heterozygous with 1 wildtype or reference allele of Ets1 (SSEts1+/-) by feeding a diet containing 4% sodium chloride for 1 week. Increases in blood pressure did not differ. However, phosphorylated ETS-1 increased in afferent arterioles of hypertensive saltsensitive rats, but not in hypertensive SSEts1+/- rats. Afferent arterioles of hypertensive salt-sensitive rats showed increased monocyte chemotactic protein-1 expression and infiltration of CD68 positive monocytes/macrophages. Isolated kidney microvessels showed increased mRNA expression of vascular cell adhesion molecule, intercellular adhesion molecule, P-selectin, fibronectin, transforming growth factor-beta, and collagen I in hypertensive salt-sensitive rats compared with hypertensive SSEts1+/- rats. Using the in vitro blood-perfused juxtamedullary nephron preparation, pressure-mediated afferent arteriolar responses were significantly blunted in hypertensive salt-sensitive rats compared to hypertensive SSEts1+/- rats. Over a 65-170 mm Hg pressure range tested baseline arteriolar diameters averaged 15.1 mm and remained between 107% and 89% of baseline diameter in hypertensive salt-sensitive rats vs. 114% and 73% in hypertensive SSEts1+/- rats (significantly different). Thus, ETS-1 participates in renal arteriolar pathology and autoregulation and thereby is involved in hypertension-mediated kidney injury in salt-sensitive rats.