Angiotensin II (Ang II) plays a major role in the pathogenesis of end-organ injury in hypertension via its diverse hemodynamic and nonhemodynamic effects. Erythroblastosis virus E26 oncogen homolog-1 (ETS-1) is an important transcription factor recently recognized as an important mediator of cell proliferation, inflammation, and fibrosis. In the present studies, we tested the hypothesis that ET...

Many of the Ets proteins have been shown to be transcription activators. In vitro, Ets 1 proteins are involved in the transcriptional induction of genes such as stromelysin 1, collagenase 1 or urokinase type plasminogen activator, which are proteases responsible for extracellular matrix degradation. In vivo, c-ets 1 is expressed in a wide variety of embryonic tissues in migrating cells, especia...

Male strain A/J mice were exposed for 6 h a day, 5 days a week to environmental tobacco smoke (ETS) generated from Kentucky 1R4F reference cigarettes. Chamber concentrations were 87 mg/m3 of total suspended particulate matter (TSP), 246 p.p.m. of CO and 16 mg/m3 of nicotine. After 5 months, 33% of the ETS exposed and 11% of the control animals had one or several lung tumors; the difference was ...

Ets-1, which stimulates metalloproteinase gene transcription, has a key role in angiogenesis. We first examined whether activated polymorphonuclear leukocytes (PMNs) enhanced angiogenesis through the induction of Ets-1. Addition of activated PMNs to endothelial cells stimulated both in vitro angiogenesis in collagen gel and Ets-1 expression. Both angiogenesis and Ets-1 expression induced by PMN...

Auto-inhibition is a common transcriptional control mechanism that is well characterized in the regulatory transcription factor Ets-1. Autoinhibition of Ets-1 DNA binding works through an inhibitory module that exists in two conformations. DNA binding requires a change in the inhibitory module from the packed to disrupted conformation. This structural switch provides a mechanism to tightly regu...

Household environmental tobacco smoke (ETS) exposure accounts for substantial morbidity among young children, but the ETS-associated morbidity burden among school-age children is less well defined. Illness-related school absenteeism is a measure of a broad spectrum of adverse effects of ETS exposure in school-age children. The authors investigated the relations between ETS exposure, asthma stat...

Modulation of VEGFR-3 expression is important for altering lymphatic endothelial cell (LEC) characteristics during the lymphangiogenic processes that occur under developmental, physiological, and pathological conditions. However, the mechanisms underlying the modulation of Vegfr3 gene expression remain largely unknown. Using genetically engineered mice and LECs, we demonstrated previously that ...

To achieve proper spatiotemporal control of gene expression, transcription factors cooperatively assemble onto specific DNA sequences. The ETS domain protein monomer of GABPα and the B-ZIP domain protein dimer of CREB1 cooperatively bind DNA only when the ETS ((C)/GCGGAA GT: ) and CRE ( GT: GACGTCAC) motifs overlap precisely, producing the ETS↔CRE motif ((C)/GCGGAA GT: GACGTCAC). We designed a ...

Regulatory T cells (T reg cells) constitute a population of CD4(+) T cells that limits immune responses. The transcription factor Foxp3 is important for determining the development and function of T reg cells; however, the molecular mechanisms that trigger and maintain its expression remain incompletely understood. In this study, we show that mice deficient for the Ets-1 transcription factor (E...

Angiotensin (Ang) II is a potent mediator of vascular inflammation. A central mechanism by which Ang II promotes inflammation is through the generation of reactive oxygen species (ROS). In the current study, we investigated the role of the transcription factor Ets-1 in regulating Ang II–induced ROS generation. ROS generation was measured in the thoracic aorta of Ets-1 / mice compared with litte...