Endothelial cell mitogenesis induced by LPA: Inhibition by thrombospondin-1 and thrombospondin-2
Endothelial cell mitogenesis induced by LPA: Inhibition by thrombospondin-1 and thrombospondin-2
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DOI：
10.1016/s0022-2143(97)90141-4
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发表时间：
1997-02-01
期刊：
影响因子：
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通讯作者：
Mosher, DF
中科院分区：
文献类型：
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作者：
Panetti, TS;Chen, H;Mosher, DF
我们研究了血小板spontin -1 （TSP1）和血小板spontin -2 （TSP2）对牛主动脉内皮（BAE）细胞摄取氚化胸苷的影响，以响应两种生长因子，碱性成纤维细胞生长因子（bFGF）和溶血磷脂酸（LPA）。bFGF和LPB通过具有趋同信号通路的不同受体刺激细胞增殖。刺激BAE细胞增殖的LPA剂量为1至30 μ mol/L，而刺激人包皮成纤维细胞增殖所需的浓度为5至100 μ mol/L，此前未见报道。从血小板中纯化的人TSP1或具有类似剂量反应的重组源抑制了基线有丝分裂活性和bFGF或LPA对BAE细胞刺激的活性。这些结果表明，血小板TSP1的抗增殖作用不是由受刺激血小板的污染物引起的。重组小鼠TSP2在与TSP1相似的剂量范围内抑制LPA对BAE细胞的增殖。由于TSP2不能激活潜伏的TGF β 1 (Schultz-Cherry et al., J Biol Chem 1995;270: 7304)，这些结果表明，TSP2抑制血管生成与控制TGF β的激活无关。总之，这些研究表明，TSP1和TSP2共有的结构基序抑制内皮细胞的增殖。此外，TSR还抑制两种生长因子受体通过不同的信号通路刺激的细胞增殖。
We examined the effects of thrombospondin-1 (TSP1) and thrombospondin-2 (TSP2) on the uptake of tritiated thymidine by bovine aortic endothelial (BAE) cells in response to two growth factors, basic fibroblast growth factor (bFGF) and lysophosphatidic acid (LPA). bFGF and LPB stimulate cell proliferation through distinct receptors that have convergent signaling pathways. The doses of LPA that trigger proliferation of BAE cells, which have not been reported previously, were 1 to 30 mu mol/L, as opposed to the 5 to 100 mu mol/L concentrations required to stimulate proliferation of human foreskin fibroblasts. Baseline mitogenic activity and activity stimulated by either bFGF or LPA on BAE cells was inhibited by human TSP1 purified from platelets or a recombinant source with a similar dose response. These results demonstrate that the anti-proliferative effect of platelet TSP1 is not caused by contaminants from the stimulated platelet. Recombinant mouse TSP2 inhibited BAE cell proliferation in response to LPA in a dose range similar to that of TSP1. Inasmuch ms TSP2 doss not activate latent TGF beta 1 (Schultz-Cherry et al., J Biol Chem 1995;270: 7304), these results show that inhibition of angiogenesis by TSPs is not related to control of activation of TGF beta. Together, these studies suggest that structural motifs common to TSP1 and TSP2 inhibit endothelial cell proliferation. Furthermore, TSR inhibit cell proliferation stimulated by two growth factor receptors that act through distinct signaling pathways.