Lysophosphatidic acid and EGF stimulate mitogenesis in human airway smooth muscle cells
Lysophosphatidic acid and EGF stimulate mitogenesis in human airway smooth muscle cells
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DOI：
10.1152/ajplung.1997.273.1.l10
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发表时间：
1997-07-01
影响因子：
4.9
通讯作者：
Toews, ML
中科院分区：
文献类型：
--
作者：
Cerutis, DR;Nogami, M;Toews, ML
气道平滑肌增殖增强被认为是哮喘和其他阻塞性呼吸道疾病的发病机制之一。溶血磷脂酸(LPA)是一种简单的生物活性脂质介质，可刺激成纤维细胞和其他一些细胞的有丝分裂。通过[H-3]胸腺嘧啶核苷掺入细胞DNA的方法检测LPA对培养的人气道平滑肌细胞有丝分裂的影响。LPA对[H-3]胸腺嘧啶核苷掺入有浓度依赖性的刺激作用，其幅度与血清相似，50mU M LPA的作用与5%血清相似。在暴露于百日咳毒素的细胞中，LPA和血清的刺激几乎完全消除，这表明百日咳毒素敏感的G蛋白参与了这些药物的有丝分裂信号转导。表皮生长因子(EGF)的刺激作用与LPA相似，但对百日咳毒素不敏感。当LPA和EGF加在一起时，对[H-3]胸腺嘧啶核苷掺入有明显的协同刺激作用，通常比单独使用这两种药物的刺激作用大10倍。LPA和EGF也通过细胞生长来刺激有丝分裂，并且LPA和EGF一起显示出协同作用。这些结果提示，LPA单独或通过增强其他生长因子的作用刺激气道平滑肌细胞的增殖，可能在正常的气道重塑或各种呼吸道疾病的平滑肌的病理性增殖中发挥作用。
Enhanced proliferation of airway smooth muscle is thought to contribute to the pathogenesis of asthma and other obstructive airway diseases. Lysophosphatidic acid (LPA) is a simple bioactive lipid mediator that stimulates mitogenesis in fibroblasts and some other cell types. The effects of LPA on mitogenesis of cultured human airway smooth muscle cells were determined by measuring [H-3]thymidine incorporation into cellular DNA. LPA induced a concentration-dependent stimulation of [H-3]thymidine incorporation of a similar magnitude to that induced by serum, with the effects of 50 mu M LPA being similar to those of 5% serum. Stimulation by LPA and by serum was almost completely eliminated in cells exposed to pertussis toxin, indicating involvement of a pertussis toxin-sensitive G protein in mitogenic signaling by these agents. Epidermal growth factor (EGF) induced stimulation of a similar magnitude as that with LPA, but the stimulation by EGF was insensitive to pertussis toxin. LPA and EGF, when added together, exhibited a markedly synergistic stimulation of [H-3]thymidine incorporation that was typically 10-fold greater than the stimulation with either agent alone. LPA and EGF also stimulated mitogenesis assessed by cell growth, and again LPA and EGF together exhibited synergism. These results suggest the possibility that stimulation of airway smooth muscle cell proliferation by LPA, either alone or by enhancing effects of other growth factors, could play a role in normal airway remodeling or in the pathological proliferation of smooth muscle in various airway diseases.