Hypoxia increases thrombospondin-1 transcript and protein in cultured endothelial cells
Hypoxia increases thrombospondin-1 transcript and protein in cultured endothelial cells
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DOI：
10.1016/s0022-2143(98)90131-7
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发表时间：
1998-12-01
期刊：
影响因子：
--
通讯作者：
Faller, DV
中科院分区：
文献类型：
--
作者：
Phelan, MW;Forman, LW;Faller, DV
内皮细胞暴露于缺氧环境会调节许多基因的表达，这些基因具有对血管组织具有血管活性或促有丝分裂的产物，包括血小板衍生生长因子、内皮素-1和内皮一氧化氮合酶。缺氧还可以改变内皮细胞对多种血细胞类型的粘附特性。 Thrombospondin-1 (TSP-1) 是一种糖蛋白，在细胞粘附和血管平滑肌增殖和迁移中起主要作用。我们在此报道缺氧诱导 TSP-1 基因和蛋白质表达。小于或等于 30 托的氧张力导致 TSP-1 转录诱导在 1 至 6 小时内开始明显，在人和牛内皮细胞中在 24 至 48 小时内达到最大诱导（6.5 倍+/- 1.2 倍）。连续缺氧 72 小时后，TSP-1 蛋白水平仍然升高。 TSP-1 稳态转录水平的诱导在很大程度上（如果不是完全）是由 TSP-1 mRNA 的转录后稳定引起的。缺氧引起的 TSP-1 诱导是一种分级且可逆的生理反应，可以通过使用氯化钴或抑制一氧化氮产生来模拟，这表明含血红素的氧传感器的参与以及内源性一氧化氮的产生在 TSP-1 调节中的作用。精氨酸丁酸盐完全抑制缺氧对 TSP-1 转录物的稳定和 TSP-1 蛋白产生的刺激的影响。
The exposure of endothelial cells to hypoxic environments regulates the expression of a number of genes with products that are vasoactive or mitogenic for vascular tissue, including platelet-derived growth factor, endothelin-1, and endothelial nitric oxide synthase. Hypoxia is also known to alter the adhesive properties of endothelium toward a variety of blood cell types. Thrombospondin-1 (TSP-1) is a glycoprotein with major roles in cellular adhesion and vascular smooth muscle proliferation and migration. We report here that hypoxia induces TSP-1 gene and protein expression. Oxygen tensions of less than or equal to 30 torr resulted in TSP-1 transcript induction initially apparent at 1 to 6 hours, with maximal induction (6.5-fold +/- 1.2-fold) within 24 to 48 hours in both human and bovine endothelial cells. TSP-1 protein levels remain elevated after 72 hours of continuous hypoxic exposure. The induction of TSP-1 steady-state transcript levels is caused in large part, if not entirely by post-transcriptional stabilization of the TSP-1 mRNA. The TSP-1 induction by hypoxia is a graded and reversible physiologic response and can be mimicked by the use of cobalt chloride or the inhibition of nitric oxide production, suggesting both the involvement of a heme-containing oxygen sensor and a role for the endogenous production of nitric oxide in TSP-1 regulation. The effects of hypoxia both on the stabilization of the TSP-1 transcript and the stimulation of TSP-1 protein production are completely inhibited by arginine butyrate.