Kaji T, Yamamoto C, Sakamoto M, Kozuka H, Koizumi F
Department of Environmental Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Life Sci. 1994;54(21):1563-9. doi: 10.1016/0024-3205(94)90027-2.
We investigated the release of plasminogen activator inhibitor type 1 (PAI-1) from cultured vascular endothelial cells after exposure to basic fibroblast growth factor (bFGF). Treatment with human recombinant bFGF of confluent cultures of endothelial cells derived from human umbilical vein resulted in a reduction of the accumulation of PAI-1 antigen (PAI-1:Ag) in the conditioned medium. The suppressive effect of bFGF completely disappeared in the presence of anti-bFGF antibody. The reduction of endothelial PAI-1:Ag release induced by bFGF was suggested to be independent of intracellular accumulation of cyclic AMP. On the other hand, nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase pathway of arachidonic acid metabolism, suppressed the spontaneous release of PAI-1:Ag by itself; in the presence of NDGA, bFGF failed to further suppress the PAI-1:Ag release. The effect of bFGF and indomethacin, an inhibitor of the cyclooxygenase pathway, was additive on the PAI-1:Ag release. The present data suggest that bFGF reduces the endothelial PAI-1:Ag release via suppression of the putative lipoxygenase pathway which up-regulates a part of the spontaneous PAI-1:Ag release.
我们研究了培养的血管内皮细胞在暴露于碱性成纤维细胞生长因子（bFGF）后纤溶酶原激活物抑制剂1型（PAI-1）的释放情况。用人重组bFGF处理源自人脐静脉的汇合内皮细胞培养物，导致条件培养基中PAI-1抗原（PAI-1:Ag）的积累减少。在抗bFGF抗体存在的情况下，bFGF的抑制作用完全消失。bFGF诱导的内皮PAI-1:Ag释放减少被认为与细胞内环磷酸腺苷的细胞内积累无关。另一方面，去甲二氢愈创木酸（NDGA），一种花生四烯酸代谢脂氧合酶途径的抑制剂，自身抑制PAI-1:Ag的自发释放；在NDGA存在的情况下，bFGF未能进一步抑制PAI-1:Ag的释放。bFGF和吲哚美辛（一种环氧化酶途径的抑制剂）对PAI-1:Ag释放的作用是相加的。目前的数据表明，bFGF通过抑制假定的脂氧合酶途径来减少内皮PAI-1:Ag的释放，该途径上调了部分PAI-1:Ag的自发释放。
