STUDIES ON BINDING AND MITOGENIC EFFECT OF INSULIN AND INSULIN-LIKE GROWTH FACTOR-I IN GLOMERULAR MESANGIAL CELLS
STUDIES ON BINDING AND MITOGENIC EFFECT OF INSULIN AND INSULIN-LIKE GROWTH FACTOR-I IN GLOMERULAR MESANGIAL CELLS
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DOI：
10.1210/endo-122-6-2788
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发表时间：
1988-06-01
期刊：
影响因子：
4.8
通讯作者：
STRIKER, GE
中科院分区：
文献类型：
--
作者：
CONTI, FG;STRIKER, LJ;STRIKER, GE
系膜细胞作为其平滑肌细胞功能的一部分，积极参与调节肾小球血流动力学。它们的上层内皮是有孔的；因此，这些细胞直接暴露于血浆物质，包括胰岛素和胰岛素样生长因子 I (IGF-I) 等激素。这些肽可能导致肾小球膜硬化和细胞增生，这是糖尿病肾小球病的特征。我们在此报告了受体的特征以及 IGF-I 和胰岛素对培养的小鼠肾小球系膜细胞的促有丝分裂作用。 IGF-I 受体在完整细胞上进行了表征。 IGF-I受体的Kd为1.47倍。 10-9 M，估计位点数量为 64,000 个受体/细胞。这种结合是时间、温度和 pH 值依赖性的，并且受体在暴露于血清后表现出下调。不同密度的细胞上受体的表达没有变化。胰岛素的特异性结合太低，无法表征完整细胞上的胰岛素受体。然而，可以在溶解的系膜细胞的麦芽凝集素纯化制剂中鉴定胰岛素受体。该受体表现出胰岛素受体的特征，包括结合的 pH 依赖性和斯卡查德曲线图。通过将[3H]胸苷掺入DNA来测量胰岛素和IGF-I对系膜细胞的促有丝分裂作用。 IGF-I 比胰岛素更有效。对 IGF-I 刺激的半最大反应发生在 1.3 倍。 10-10 M，并且在 10-7 M 浓度范围内观察到胰岛素的类似增加，表明这种胰岛素作用是通过 IGF-I 受体介导的。这些数据表明，小鼠肾小球微血管平滑肌细胞在体外表达 IGF-I 的细胞表面受体，并且该肽是这些系膜细胞的有效有丝分裂原。因此，它可能在肾小球增殖性病变中发挥作用。胰岛素受体的数量很少，并且不介导系膜细胞的有丝分裂发生。
The mesangial cells, as part of their smooth muscle cell function, are actively involved in regulating glomerular hemodynamics. Their overlying endothelium is fenestrated; therefore, these cells are directly exposed to plasma substances, including hormones such as insulin and insulin-like growth factor I (IGF-I). These peptides may contribute to the mesangial sclerosis and cellular hyperplasia that characterize diabetic glomerulopathy. We report herein the characterization of the receptors and the mitogenic effects of IGF-I and insulin on mouse glomerular mesangial cells in culture. The IGF-I receptor was characterized on intact cells. The Kd of the IGF-I receptor was 1.47 .times. 10-9 M, and the estimated number of sites was 64,000 receptors/cell. The binding was time, temperature, and pH dependent, and the receptor showed down-regulation after exposure to serum. The expression of the receptor did not change on cells at different densities. The specific binding for insulin was too low to allow characterization of the insulin receptor on intact cells. However, it was possible to identify the insulin receptor in a wheat germ agglutinin-purified preparation of solubilized mesangial cells. This receptor showed the characteristic features of the insulin receptor, including pH dependence of binding and a curvilinear Scatchard plot. The mitogenic effects of insulin and IGF-I on mesangial cells were measured by the incorporation of [3H]thymidine into DNA. IGF-I was more potent than insulin. The half-maximal response to IGF-I stimulation occurred at 1.3 .times. 10-10 M, and a similar increase with insulin was observed at concentrations in the range of 10-7 M, suggesting that this insulin action was mediated through the IGF-I receptor. These data show that the mouse microvascular smooth muscle cells of the glomerulus express a cell surface receptor for IGF-I in vitro and that this peptide is a potent mitogen for these mesangial cells. It may, therefore, play a role in glomerular proliferative lesions. The insulin receptor is present in small numbers and does not mediate mitogenesis in mesangial cells.