Adherence-dependent increase in human monocyte PDGF(B) mRNA is associated with increases in c-fos, c-jun, and EGR2 mRNA.
Adherence-dependent increase in human monocyte PDGF(B) mRNA is associated with increases in c-fos, c-jun, and EGR2 mRNA.
复制标题
人单核细胞PDGF（B）mRNA的依赖性增加与C-FOS，C-JUN和EGR2 mRNA的增加有关。
DOI：
10.1083/jcb.111.5.2139
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发表时间：
1990-11
影响因子：
7.8
通讯作者：
Clark, R A
中科院分区：
文献类型：
--
作者：
Shaw, R J;Doherty, D E;Ritter, A G;Benedict, S H;Clark, R A
黏附是循环单核细胞向组织巨噬细胞转变的重要初始步骤。这种差异化伴随着产生增长因子的能力的增强。我们假设黏附本身可能是一系列基因激活的重要触发因素，最终导致编码促纤维化生长因子的mRNA增加，如血小板衍生生长因子B亚单位(PDGF[B])和转化生长因子-β(TGF-β)。体外贴壁后，人单核细胞PDGF(B)基因表达呈双相增加，高峰出现在6h和13d，而转化生长因子-β基因表达未见增加。细胞松弛素D破坏细胞骨架的完整性后，PDGF(B)的6h表达增加不受单核细胞刺激脂多糖存在的影响。无论是纤维连接蛋白还是胶原涂层塑料的黏附对PDGF(B)mRNA的积累几乎没有一致的影响。在贴壁单核细胞中观察到PDGF(B)mRNA的增加伴随着早期生长反应基因c-fos(在20min达到最大)、c-jun和EGR2(在6-24 h达到最大)的mRNAs的增加。细胞松弛素D抑制c-jun和EGR2的表达，但不抑制c-fos的表达。这些结果表明，黏附导致c-fos、c-jun、EGR2和PDGF(B)的表达增加。此外，c-jun、EGR2和PDGF(B)的升高可能依赖于细胞骨架重排。在粘连时对这些事件的调制提供了一种机制，通过该机制可以实现细胞的差异化启动。
Adherence is an important initial step in the transition of a circulating monocyte to a tissue macrophage. This differentiation is accompanied by an augmented capacity to generate growth factors. We hypothesized that adherence itself might be an important trigger for a sequence of gene activation culminating in cells with increased mRNA encoding profibrotic growth factors such as platelet-derived growth factor B subunit (PDGF[B]) and transforming growth factor-beta (TGF- beta). After in vitro adherence, human monocytes had a biphasic increase in PDGF(B) mRNA with peaks at 6 h and 13 d. No increase in TGF- beta mRNA was observed. The 6-h increase in PDGF(B) mRNA was adherence dependent, and in addition, was abrogated when the cytoskeletal integrity was compromised by cytochalasin D. The 6-h increase in PDGF(B) mRNA was unaltered by adherence in the presence of the monocyte stimulus lipopolysaccharide. Adherence to either fibronectin or collagen-coated plastic had little consistent effect on PDGF(B) mRNA accumulation. The increased PDGF(B) mRNA observed in adherent monocytes was accompanied by increases in mRNAs of the early growth response genes c-fos (maximal at 20 min), c-jun, and EGR2 (maximal at 6-24 h). The increase in c-jun and EGR2, but not c-fos, mRNA was also abrogated by cytochalasin D. These observations suggest that adherence results in increases of c-fos, c-jun, EGR2, and PDGF(B) mRNA. In addition, the increases in c-jun, EGR2, and PDGF(B) may depend on cytoskeletal rearrangement. Modulation of these events at the time of adherence offers a mechanism by which differential priming of the cells may be accomplished.