INDUCTION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR GENE-EXPRESSION BY INTERLEUKIN-1-BETA IN RAT AORTIC SMOOTH-MUSCLE CELLS
INDUCTION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR GENE-EXPRESSION BY INTERLEUKIN-1-BETA IN RAT AORTIC SMOOTH-MUSCLE CELLS
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DOI：
10.1074/jbc.270.1.308
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发表时间：
1995-01-06
影响因子：
4.8
通讯作者：
LEE, ME
中科院分区：
文献类型：
--
作者：
LI, J;PERRELLA, MA;LEE, ME
血管内皮生长因子（VEGF）是一种强有力的特异性促血管内皮细胞有丝分裂原，在体内可促进新生血管形成。为了确定是否白细胞介素-1 β（IL-1 β），这是目前在动脉粥样硬化病变，诱导血管平滑肌细胞VEGF基因表达，我们进行了RNA印迹分析大鼠主动脉平滑肌细胞（RASMC）与大鼠VEGF cDNA探针。IL-1 β以时间和剂量依赖性方式增加RASMC中VEGF mRNA的水平。低至0.1 ng/ml IL-1 β可使VEGF mRNA水平增加5倍，10 ng/ml IL-1 β可使VEGF mRNA增加4倍。我们还测量了VEGF mRNA的半衰期，并在加入IL-1 β之前和之后进行了核运行实验，以观察IL-1 β是否通过稳定mRNA或通过增加其转录速率来增加VEGF mRNA水平。IL-1 β使RASMC中VEGF mRNA的正常2小时半衰期延长至3.2小时（60%），IL-1 β使VEGF基因转录速率增加2.1倍。在VEGF特异性抗体的免疫印迹实验中，我们发现IL-1 β使RASMC中的VEGF蛋白水平增加了3.3倍。这些数据共同表明IL-1 β诱导平滑肌细胞中VEGF基因表达。这种IL-1 β诱导的VEGF表达可能通过促进新血管的发育而加速动脉粥样硬化病变的进展。
Vascular endothelial growth factor (VEGF) is a potent and specific mitogen for vascular endothelial cells and promotes neovascularization in vivo. To determine whether interleukin-1 beta (IL-1 beta), which is present in atherosclerotic lesions, induces VEGF gene expression in vascular smooth muscle cells, we performed RNA blot analysis on rat aortic smooth muscle cells (RASMC) with a rat VEGF cDNA probe. IL-1 beta increased VEGF mRNA levels in RASMC in a time- and dose-dependent manner. As little as 0.1 ng/ml IL-1 beta increased VEGF mRNA levels by S-fold and 10 ng/ml IL-1 beta increased VEGF mRNA by 4-fold. We also measured the half-life of VEGF mRNA and performed nuclear run on experiments before and after addition of IL-1 beta to see if IL-1 beta increased VEGF mRNA levels by stabilizing the mRNA or by increasing its rate of transcription. The normal, 2-h half-life of VEGF mRNA in RASMC was lengthened to 3.2 h (60%) by IL-1 beta, and IL-1 beta increased the rate of VEGF gene transcription by 2.1-fold. In immunoblot experiments with an antibody specific for VEGF, we found that IL-1 beta increased VEGF protein levels in RASMC by 3.3-fold. Together these data indicate that IL-1 beta induces VEGF gene expression in smooth muscle cells. This IL-1 beta-induced expression of VEGF may accelerate the progression of atherosclerotic lesions by promoting the development of new blood vessels.