Tsai J C, Liu L, Guan J, Aird W C
Department of Molecular Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Am J Physiol Cell Physiol. 2000 Nov;279(5):C1414-24. doi: 10.1152/ajpcell.2000.279.5.C1414.
The early growth response (Egr)-1 transcription factor serves to couple changes in the extracellular environment to alterations in gene expression. An understanding of the mechanisms that underlie Egr-1 gene regulation should provide important insights into how environmental signals are transduced by endothelial cells. The aim of the present study was to determine whether epidermal growth factor (EGF) induces Egr-1 expression in endothelial cells. In ECV304 cells, Egr-1 mRNA and protein levels were increased in response to EGF. In stable transfection assays, the 1,200-bp promoter of the mouse Egr-1 gene contained information for EGF response via a protein kinase C-independent, mitogen-activated protein kinase-dependent pathway. The endogenous Egr-1 gene was similarly responsive to EGF in primary human umbilical vein endothelial cells, human coronary artery endothelial cells, and rat fat pad endothelial cells, but not in bovine aortic endothelial cells, calf pulmonary artery endothelial cells, or PY-4-1 endothelial cells. Together, these results suggest that the Egr-1 gene is responsive to EGF in a subset of endothelial cells.
早期生长反应（Egr）-1转录因子可将细胞外环境的变化与基因表达的改变联系起来。了解Egr-1基因调控的潜在机制应能为内皮细胞如何转导环境信号提供重要见解。本研究的目的是确定表皮生长因子（EGF）是否能诱导内皮细胞中Egr-1的表达。在ECV304细胞中，Egr-1的mRNA和蛋白质水平会因EGF而升高。在稳定转染试验中，小鼠Egr-1基因的1200bp启动子通过一条不依赖蛋白激酶C、依赖丝裂原活化蛋白激酶的途径包含了对EGF反应的信息。内源性Egr-1基因在原代人脐静脉内皮细胞、人冠状动脉内皮细胞和大鼠脂肪垫内皮细胞中同样对EGF有反应，但在牛主动脉内皮细胞、小牛肺动脉内皮细胞或PY-4-1内皮细胞中则无反应。总之，这些结果表明Egr-1基因在一部分内皮细胞中对EGF有反应。
