Cyclooxygenase gene expression is down-regulated by heparin-binding (acidic fibroblast) growth factor-1 in human endothelial cells.
Cyclooxygenase gene expression is down-regulated by heparin-binding (acidic fibroblast) growth factor-1 in human endothelial cells.
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DOI：
10.1016/s0021-9258(18)54392-1
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发表时间：
1991-12
期刊：
影响因子：
--
通讯作者：
T. Hla;T. Maciag
中科院分区：
文献类型：
--
作者：
T. Hla;T. Maciag
环氧合酶（EC 1.14.99.1，考克斯）是炎性前列腺素类生物合成中的限速酶，其表达受生长因子和细胞因子调节。我们以前已经表明，细胞因子白细胞介素-1，在体外内皮细胞生长的抑制剂和前列环素的生产刺激剂，诱导3-羟化酶考克斯转录在培养的人脐静脉内皮细胞（HUVEC）的表达。相反，内皮细胞有丝分裂原肝素结合（酸性成纤维细胞）生长因子-1（HBGF-1）抑制HUVEC中前列环素的合成。在本报告中，我们描述了HBGF-1对HUVEC中考克斯mRNA表达的影响。在HBGF-1存在下培养的细胞表达降低的考克斯mRNA水平，而在血清中维持的静止细胞表达高7倍的考克斯转录物水平。同时，考克斯翻译产物和前列环素合成的水平也被HBGF-1降低。此外，在肝素存在下，HBGF-1以剂量和时间依赖性方式下调考克斯转录物的水平。HBGF-1的起效缓慢，需要长达24小时才能抑制考克斯mRNA的水平。最后，HBGF-1抑制考克斯mRNA水平的有效剂量与有丝分裂所需的剂量相似，表明体外降低考克斯表达可能需要细胞增殖。因此，考克斯可能属于一类在内皮细胞增殖期间可逆下调的基因。
The expression of cyclooxygenase (EC 1.14.99.1, Cox), a rate-limiting enzyme in the biosynthesis of inflammatory prostanoids, is regulated by growth factors and cytokines. We have shown previously that the cytokine interleukin-1, an inhibitor of endothelial growth in vitro and stimulator of prostacyclin production, induces the expression of the 3-kilobase Cox transcript in cultured human umbilical vein endothelial cells (HUVEC). In contrast, the endothelial cell mitogen, heparin-binding (acidic fibroblast) growth factor-1 (HBGF-1) inhibits the synthesis of prostacyclin in HUVEC. In this report, we describe the effect of HBGF-1 on Cox mRNA expression in HUVEC. Cells cultured in the presence of HBGF-1 express diminished Cox mRNA levels whereas quiescent cells maintained in serum expressed a 7-fold higher level of the transcript for Cox. Concomitantly, the level of the Cox translation product and prostacyclin synthesis are also reduced by HBGF-1. Further, HBGF-1, in the presence of heparin, down-regulates the levels of the Cox transcript in a dose- and time-dependent manner. The onset of action of HBGF-1 is slow, requiring up to 24 h to depress the level of Cox mRNA. Lastly, the effective dose of HBGF-1 to depress Cox mRNA levels is similar to that required for mitogenesis, suggesting that cell proliferation may be required for the reduction of Cox expression in vitro. Thus, Cox may belong to a class of genes that are reversibly down-regulated during periods of endothelial cell proliferation.