Effect of thrombin on proliferation, contraction and prostaglandin production of rat glomerular mesangial cells in culture.
Effect of thrombin on proliferation, contraction and prostaglandin production of rat glomerular mesangial cells in culture.
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凝血酶对培养的大鼠肾小球系膜细胞增殖、收缩和前列腺素产生的影响。
DOI：
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发表时间：
1992
影响因子：
3.5
通讯作者：
T. Groom
中科院分区：
文献类型：
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作者：
C. Albrightson;P. Nambi;B. Zabko;G. Dytko;T. Groom
研究了凝血酶对系膜细胞功能的影响。凝血酶引起大鼠肾小球系膜细胞[3H]胸苷结合（EC50 = 0.36 +/- 0.09 U/ml）、细胞内钙[(ca++)i]动员（EC50 = 1.9 +/- 0.5 U/ml）和前列腺素E2 （PGE2）产生（EC50 = 0.25 +/- 0.02 U/ml）的剂量依赖性增加。这些作用被凝血酶抑制剂水蛭素（KB = 10.4 +/- 0.2 nM）阻断。通过在系膜细胞培养中加入钙通道阻滞剂硝苯地平和环氧化酶抑制剂吲哚美辛，测试了（Ca++）i动员和花生四烯酸酯代谢在凝血酶刺激增殖中的作用。在完全抑制凝血酶介导的PGE2生成的剂量下，吲哚美辛对增殖没有显著影响。钙离子通道阻滞剂硝苯地平以剂量依赖性的方式抑制PGE2的产生和[3H]胸腺嘧啶的结合，但仅在被认为是非特异性的浓度下。凝血酶除了对PGE2、胸苷结合和Ca++动员的影响外，还通过底物扭曲技术确定了凝血酶引起系膜细胞收缩。这种作用不受吲哚美辛的抑制。这些结果表明凝血酶可以在体外改变系膜细胞的功能。
The effect of thrombin on mesangial cell function was investigated. Thrombin caused a dose-dependent increase in [3H] thymidine incorporation (EC50 = 0.36 +/- 0.09 U/ml), intracellular calcium [(Ca++)i] mobilization (EC50 = 1.9 +/- 0.5 U/ml) and prostaglandin E2 (PGE2) production (EC50 = 0.25 +/- 0.02 U/ml) in rat glomerular mesangial cells. These effects were blocked by the thrombin inhibitor, hirudin (KB = 10.4 +/- 0.2 nM). The role of (Ca++)i mobilization and arachidonate metabolism in thrombin-stimulated proliferation was tested by the addition of the calcium channel blocker, nifedipine, and the cyclooxygenase inhibitor, indomethacin, to mesangial cell cultures. Indomethacin, at doses that completely inhibited the thrombin-mediated production of PGE2, had no significant effect on proliferation. The Ca++ channel blocker, nifedipine, inhibited both PGE2 production and [3H] thymidine incorporation in a dose-dependent fashion, but only at concentrations considered nonspecific. In addition to its effects on PGE2, thymidine incorporation and Ca++ mobilization, thrombin caused mesangial cell contraction as determined by a substrate distortion technique. This effect was not inhibited by indomethacin. These results indicate that thrombin can alter mesangial cell function in vitro.