Regulation of human mesangial cell growth in culture by thromboxane A2 and prostacyclin.
Regulation of human mesangial cell growth in culture by thromboxane A2 and prostacyclin.
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血栓素 A2 和前列环素对培养物中人系膜细胞生长的调节。
DOI：
10.1038/ki.1990.191
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发表时间：
1990
影响因子：
19.6
通讯作者：
Dunn,MJ
中科院分区：
文献类型：
--
作者：
Menè,P;Abboud,HE;Dunn,MJ
血栓素A2和前列环素对培养的人肾小球系膜细胞生长的调节类二十烷酸生物合成升高是某些形式的人类和实验性肾小球增生性疾病的特征。血栓素A2（TxA 2）和其他前列腺素（PG）通过特异性受体和细胞内信号转导机制作用于人肾小球系膜细胞。我们研究了U-46619（一种刺激系膜磷脂酶C的TxA_2模拟物）和PGI_2类似物（一种腺苷酸环化酶的有效激活剂）对培养的人肾小球系膜细胞增殖的作用。当单独应用于静止细胞时，U-46619仅具有弱的促有丝分裂活性，如通过[3 H]胸苷（[3 H]-TdR）掺入和细胞计数所评估。另一方面，在用1 - 17%胎牛血清（FBS）刺激细胞24小时前10分钟加入U-46619，可有效且剂量依赖性地抑制FBS刺激的[3 H]-TdR掺入。同样，U-46619抑制10 ng/ml血小板衍生生长因子（PDGF）、表皮生长因子或碱性成纤维细胞生长因子对[3 H]-TdR掺入的影响，分别为55%、79%和88%。U-46619的作用没有被磷脂酶C的另一种刺激物血管紧张素II模仿。伊洛前列素还抑制FBS激活的增殖。无论是花生酸抑制FBS或PDGF诱导的细胞内Ca ~（2+）升高。TxA 2和伊洛前列素在培养细胞中的作用表明类花生酸和生长因子在控制系膜细胞增殖中的多功能相互作用。1
Regulation of human mesangial cell growth in culture by thromboxane A2and prostacyclin. Elevated eicosanoid biosynthesis characterizes certain forms of human and experimental glomerular proliferative disease. Thromboxane A2(TxA2) and other prostaglandins (PG) act through specific receptors and mechanisms of intracellular signal transduction in human mesangial cells. We studied the actions of U-46619, a TxA2mimetic which stimulates mesangial phospholipase C, and of the PGI2analogue, Iloprost, a potent activator of adenylate cyclase, on proliferation of cultured human mesangial cells. When applied alone to quiescent cells, U-46619 had only weak mitogenic activity, as assessed by [3H]thymidine ([3H]-TdR) incorporation and cell counts. On the other hand, addition of U-46619 10 minutes prior to stimulation of the cells with 1 to 17% fetal bovine serum (FBS) for 24 hours, potently and dose-dependently inhibited FBS-stimulated [3H]-TdR incorporation. Similarly, U-46619 inhibited the effects of 10 ng/ml platelet-derived growth factor (PDGF), epidermal growth factor or basic fibroblast growth factor on [3H]-TdR incorporation, by 55, 79 and 88%, respectively. The effects of U-46619 were not mimicked by another stimulus of phospholipase C, angiotensin II. Iloprost also inhibited FBS-activated proliferation. Neither eicosanoid inhibited the rise of cytosolic Ca2+induced by FBS or PDGF. The actions of TxA2and Iloprost in cultured cells point to multiple functional interactions between eicosanoids and growth factors in the control of mesangial cell proliferation.1