Pulsatile and steady flow induces c‐fos expression in human endothelial cells
Pulsatile and steady flow induces c‐fos expression in human endothelial cells
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DOI：
10.1002/jcp.1041540118
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发表时间：
1993-01
影响因子：
5.6
通讯作者：
H. Hsieh;Nan‐qian Li;J. Frangos
中科院分区：
文献类型：
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作者：
H. Hsieh;Nan‐qian Li;J. Frangos
研究了脉动流和稳态流对培养的人脐静脉内皮细胞（HUVEC）中原癌基因c-fos、c-jun和c-myc mRNA水平的影响。静止培养中的c-fos mRNA水平非常低。平均剪切应力为16 dynes/cm 2的1 Hz脉动流在血流开始后0.5 h诱导HUVEC中c-fos mRNA水平急剧增加，并在1 h内迅速下降至基础水平。具有类似剪切应力的稳定流动也诱导c-fos mRNA水平的瞬时增加，但程度较小。此外，当低剪切力（2-6达因/cm 2）被高剪切力（16-33达因/cm 2）取代时，观察到c-fos mRNA水平增加。脉动流和稳定流导致c-jun和c-myc mRNA水平略微增加。还研究了脉动性在血小板衍生生长因子（PDGF）表达中的作用。脉动流诱导PDGF A-和B-链mRNA水平一过性升高，峰值出现在1.5-2 h。脉动流在介导c-fos表达方面更具刺激性，然而，在介导PDGF表达方面的刺激性低于稳定流。通过使用各种抑制剂，发现蛋白激酶C是流动诱导的c-fos表达的重要介质，G蛋白，磷脂酶C和细胞内钙参与其中。蛋白激酶C以前被证明是流动诱导的PDGF表达中可能的主要介质，其至少部分地似乎遵循c-fos的诱导机制，这表明c-fos和PDGF诱导之间可能存在联系。然而，c-fos反义治疗，这显着抑制c-fos转录，未能阻断流动诱导的PDGF表达，表明流动诱导的c-fos表达可能在流动诱导的PDGF表达的机制中没有发挥重要作用。与稳态流相比，脉动流诱导c-fos和PDGF表达的差异表明，与稳态流相比，脉动流诱导c-fos和PDGF表达的差异表明，HUVEC中存在复杂的流动介导的基因表达调控机制。由血流介导的这些原癌基因表达的增加可能在调节长期细胞反应中很重要。© 1993 Wiley利斯公司
The effects of pulsatile and steady fluid flow on the mRNA levels of proto‐oncogenes c‐fos, c‐jun, and c‐myc in cultured human umbilical vein endothelial cells (HUVEC) were investigated. c‐fos mRNA levels in stationary cultures were very low. A 1 Hz pulsatile flow with an average shear stress of 16 dynes/cm2 induced a dramatic increase of c‐fos mRNA levels in HUVEC 0.5 h after the onset of flow, which declined rapidly to basal levels within 1 h. Steady flow with a similar shear stress also induced a transient increase of c‐fos mRNA levels, but to a lesser extent. In addition, increased, c‐fos mRNA levels were observed when low shear (2–6 dynes/cm2) was replaced by high shear (16–33 dynes/cm2). Pulsatile and steady flow caused a slight increase of c‐jun and c‐myc mRNA levels. The role of pulsatility was also investigated in platelet‐derived growth factor (PDGF) expression. Pulsatile flow induced a transient increase of PDGF A‐ and B‐chain mRNA levels with peaks at 1.5–2 h. Pulsatile flow, which was more stimulatory in mediating c‐fos expression, however, was less stimulatory than steady flow in mediating PDGF expression. By using various inhibitors, protein kinase C was found to be an important mediator in flow‐induced c‐fos expression, with the involvement of G proteins, phospholipase C, and intracellular calcium. Protein kinase C was previously shown as a possible major mediator in flow‐induced PDGF expression which, at least partly, appeared to follow the induction mechanism of c‐fos, suggesting a possible connection between c‐fos and PDGF induction. However, the c‐fos antisense treatment, which significantly inhibited c‐fos transcription, failed to block the flow‐induced PDGF expression, suggesting that flow‐induced c‐fos expression may not play an important role in the mechanism of flow‐induced PDGF expression. The difference in the induction of c‐fos and PDGF expression under pulsatile as compared to steady flow indicates of c‐fos and PDGF expression under pulsatile as compared to steady flow indicates that a complex, flow‐mediated regulatory mechanism of gene expression exists in HUVEC. The increased expression of these proto‐oncogenes mediated by flow may be important in regulating long‐term cellular responses. © 1993 Wiley‐Liss, Inc.