Regulation of fibronectin biosynthesis by dexamethasone, transforming growth factor beta, and cAMP in human cell lines.
Regulation of fibronectin biosynthesis by dexamethasone, transforming growth factor beta, and cAMP in human cell lines.
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DOI：
10.1083/jcb.106.6.2159
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发表时间：
1988-06
期刊：
影响因子：
--
通讯作者：
Bourgeois S
中科院分区：
文献类型：
--
作者：
Dean DC;Newby RF;Bourgeois S
在六种人类细胞系中检查了地塞米松（一种合成糖皮质激素）、毛喉素（腺苷酸环化酶激活剂）和转化生长因子 β (TGF-β) 对纤连蛋白 (FN) 生物合成的调节。地塞米松治疗使纤维肉瘤细胞系 HT-1080 的 FN 生物合成增加最大（约 45 倍）。这似乎是由于地塞米松介导的 FN mRNA 稳定性增加所致，这将信息半衰期从约 11 小时延长至 26 小时。与正常成纤维细胞（70小时）相比，纤维肉瘤（t1/2 11小时）中FN mRNA的相对不稳定性似乎是由HT-1080细胞的特定转化表型造成的。 Forskolin 和 TGF-beta 可增加大多数细胞系中 FN 基因的转录率。这些效应（四到六倍）迅速发生，并且不需要在包括正常成纤维细胞的反应细胞系中合成蛋白质。然而，在纤维肉瘤（HT-1080）中，观察到令人惊讶的大诱导（20-30倍），并且这种诱导与正常成纤维细胞和其他细胞系中的诱导不同，因为需要蛋白质合成和滞后期。在 HT-1080 细胞中，地塞米松与毛喉素或 TGF-β 具有协同作用，可将 FN 生物合成速率提高约 200 倍，达到与正常成纤维细胞相似的水平。这似乎是 FN mRNA 稳定（地塞米松）和转录增加（毛喉素和 TGF-β）共同作用的结果。
The regulation of fibronectin (FN) biosynthesis by dexamethasone (a synthetic glucocorticoid), forskolin (an activator of adenylate cyclase), and transforming growth factor beta (TGF-beta) was examined in six human cell lines. Dexamethasone treatment produced the largest increase in FN biosynthesis in the fibrosarcoma cell line, HT-1080 (approximately 45-fold). This seems to result from a dexamethasone- mediated increase in FN mRNA stability which increases the message half- life from approximately 11 to 26 h. The relative instability of FN mRNA in the fibrosarcoma (t1/2 11 h) compared to normal fibroblasts (70 h) appears to result from the particular transformed phenotype of the HT- 1080 cells. Forskolin and TGF-beta increase the rate of FN gene transcription in most of the cell lines. These effects (four- to six- fold) occur rapidly and do not require protein synthesis in the responsive cell lines which include normal fibroblasts. However, in the fibrosarcoma (HT-1080), a surprisingly large induction (20-30-fold) is observed and this induction is different from that in the normal fibroblasts and the other cell lines in that both protein synthesis and a lag period are required. Synergism is seen with dexamethasone and either forskolin or TGF-beta in HT-1080 cells increasing the rate of FN biosynthesis approximately 200-fold to a level similar to normal fibroblasts. This seems to result from a combination of FN mRNA stabilization (dexamethasone) and increased transcription (forskolin and TGF-beta).