Hemodynamic forces, such as fluid shear stress, that act on the endothelial lining of the cardiovascular system can modulate the expression of an expanding number of genes crucial for homeostasis and the pathogenesis of vascular disease. A 6-bp core element (5'-GAGACC-3'), defined previously as a shear-stress response element is present in the promoters of many genes, including the PDGF B-chain, whose expression is modulated by shear stress. The identity of the nuclear protein(s) binding to this element has not yet been elucidated. Using electrophoretic mobility shift assays and in vitro DNase I footprinting, we demonstrate that nuclear factor-kappa B p50-p65 heterodimers, which accumulate in the nuclei of cultured vascular endothelial cells exposed to fluid shear stress, bind to the PDGF-B shear-stress response element in a specific manner. Mutation of this binding motif abrogated its interaction with p50-p65 and abolished the ability of the promoter to mediate increased gene expression in endothelial cells exposed to shear stress. Transient cotransfection studies indicate that p50-p65 is able to activate PDGF-B shear-stress response element-dependent reporter gene expression in these cells. These findings thus implicate nuclear factor-kappa B in the transactivation of an endothelial gene responding to a defined fluid mechanical force.
L M Khachigian, N Resnick, M A Gimbrone Jr, T Collins
Usage data is cumulative from January 2019 through January 2020.
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.