Li Xiao-dong, Zu Shu-yu, Wang Wen, Zhu Guang-jin
Department of Pathophysiology, Institute of Basic Medical Sciences, CAMS, PUMC, Beijing 100005, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2003 Jun;25(3):307-11.
To study the effect of nuclear transcription factor AP-1 on tumor necrosis factor alpha (TNF-alpha) or minimal modified low density lipoprotein (mmLDL)-induced expression of plasminogen activator inhibitor-1 (PAI-1) in human vascular endothelial cells.
Using gene recombination techniques, four luciferase reporter gene plasmids containing different length of human PAI-1 gene promoter were constructed. Through the transient transfection analysis, the roles of AP-1 element (from -823 bp to -553 bp) in PAI-1 promoter have been determined. In order to further verify the role of AP-1 element, the three site-directed mutants were recovered using PCR and sequencing assay.
The induction by TNF-alpha or mmLDL were decreased markedly when the three AP-1 elements in PAI-1 promoter had been mutated respectively.
These results indicate that the AP-1 element in PAI-1 promoter may have important role in PAI-1 gene transcriptions in endothelial cells induced by TNF-alpha or mmLDL.
研究核转录因子AP - 1对肿瘤坏死因子α（TNF -α）或轻度修饰的低密度脂蛋白（mmLDL）诱导人血管内皮细胞纤溶酶原激活物抑制剂-1（PAI - 1）表达的影响。
利用基因重组技术构建了4种含不同长度人PAI - 1基因启动子的荧光素酶报告基因质粒。通过瞬时转染分析，确定了PAI - 1启动子中AP - 1元件（从-823 bp至-553 bp）的作用。为进一步验证AP - 1元件的作用，采用PCR和测序分析方法获得了3个定点突变体。
当PAI - 1启动子中的3个AP - 1元件分别发生突变时，TNF -α或mmLDL的诱导作用明显降低。
这些结果表明，PAI - 1启动子中的AP - 1元件可能在TNF -α或mmLDL诱导的内皮细胞PAI - 1基因转录中起重要作用。
