McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599‐7126, USA.
Cell Biochem Funct. 2011 Jun;29(4):334-41. doi: 10.1002/cbf.1755.
During vascular development, endothelial cells are exposed to a variety of rapidly changing factors, including fluctuating oxygen levels. We have previously shown that ankyrin repeat and suppressor of cytokine signalling box protein 4 (ASB4) is the most highly differentially expressed gene in the vascular lineage during early differentiation and is expressed in the embryonic vasculature at a time when oxygen tension is rising because of the onset of placental blood flow. To further our understanding of the regulation of ASB4 expression in endothelial cells, we tested the effect of various stressors for their ability to alter ASB4 expression in the immortalized murine endothelial cell lines MS1 and SVR. ASB4 expression is decreased during hypoxic insult and shear stress, whereas it is increased in response to tumour necrosis factor alpha (TNF-α). Further investigation indicated that nuclear factor kappa B (NF-κB) is the responsible transcription factor involved in the TNF-α-induced upregulation of ASB4, placing ASB4 downstream of NF-κB in the TNF-α signalling cascade and identifying it as a potential regulator for TNF-α's numerous functions associated with inflammation, angiogenesis and apoptosis.
在血管发育过程中，内皮细胞暴露于各种快速变化的因素中，包括氧水平的波动。我们之前已经表明，锚蛋白重复和细胞因子信号抑制盒蛋白 4（ASB4）是早期分化过程中血管谱系中表达差异最大的基因，并且在由于胎盘血流开始而氧张力升高时在胚胎血管中表达。为了进一步了解内皮细胞中 ASB4 表达的调节，我们测试了各种应激源对其改变永生化小鼠内皮细胞系 MS1 和 SVR 中 ASB4 表达的能力。在缺氧损伤和切应力下，ASB4 的表达减少，而响应肿瘤坏死因子α（TNF-α）时，ASB4 的表达增加。进一步的研究表明，核因子 kappa B（NF-κB）是参与 TNF-α诱导的 ASB4 上调的负责转录因子，将 ASB4 置于 TNF-α信号级联中的 NF-κB 下游，并将其鉴定为 TNF-α 与其炎症、血管生成和细胞凋亡相关的许多功能的潜在调节剂。
