Insulin-like growth factor-I increases astrocyte intercellular gap junctional communication and connexin43 expression in vitro
Insulin-like growth factor-I increases astrocyte intercellular gap junctional communication and connexin43 expression in vitro
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DOI：
10.1002/jnr.10734
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发表时间：
2003-10-01
影响因子：
4.2
通讯作者：
Eriksson, PS
中科院分区：
文献类型：
--
作者：
Åberg, ND;Blomstrand, F;Eriksson, PS
缝隙连接蛋白43（cx43）在星形胶质细胞中形成缝隙连接，这些缝隙连接通过提供细胞间的转运来介导细胞间的通讯。低分子量代谢物和离子。我们最近发现全身生长激素增加了大脑中的cx43。一种可能性是局部脑胰岛素样生长因子-I（IGF-I）可以通过直接作用于星形胶质细胞来介导这种效应。在本研究中，我们研究了直接应用重组人IGF-I（rhlGF-I）对原代培养的星形胶质细胞中cx43蛋白表达和间隙连接通讯（GJC）的影响。在无血清条件下用rhIGF-I刺激24小时后，分析GJC和cx43蛋白。30 ng/ml rhIGF-I可增加GJC和cx43蛋白的丰度。在此浓度下，rhIGF-I未显著增加星形胶质细胞的细胞增殖。然而，较高浓度的rhIGF-I（150 ng/ml）对GJC/ cx43没有影响，但增加细胞增殖。由于IGF结合蛋白（IGFBPs）对IGF-I作用的重要调节作用，我们分析了条件培养基中的IGFBPs。在IGFBPs（特别是IGFBP-2）丰度低的培养物中，GJC对30 ng/ml rhIGF-I的反应为81%，而平均值为25%。最后，作为对照，给予等摩尔浓度的胰岛素。然而，GJC没有受到影响，这表明rhIGF-I通过IGF-I受体发挥作用。总之，数据表明，rhIGF-I可能会增加GJC/ cx43，而更高浓度的rhIGF-I刺激增殖发生，不影响GJC/cx43。此外，IGFBP-2似乎通过旁分泌机制调节rhIGF-I对星形胶质细胞GJC的作用。(C)2003 Wiley-Liss，Inc.
Connexin43 (cx43) forms gap junctions in astrocytes, and these gap junctions mediate intercellular communication by providing transport of. low-molecular-weight metabolites and ions. We have recently shown that systemic growth hormone increases cx43 in the brain. One possibility was that local brain insulin-like growth factor-I (IGF-I) could mediate the effect by acting directly on astrocytes. In the present study, we examined the effects of direct application of recombinant human IGF-I (rhlGF-I) on astrocytes in primary culture concerning cx43 protein expression and gap junctional communication (GJC). After 24 hr of stimulation with rhIGF-I under serum-free conditions, the GJC and cx43 protein were analyzed. Administration of 30 ng/ml rhIGF-I increased the GJC and the abundance of cx43 protein. Cell proliferation of the astrocytes was not significantly increased by rhIGF-I at this concentration. However, a higher concentration of rhIGF-I (150 ng/ml) had no effect on GJC/ cx43 but increased cell proliferation. Because of the important modulatory role of IGF binding proteins (IGFBPs) on IGF-I action, we analyzed IGFBPs in conditioned media. In cultures with a low abundance of IGFBPs (especially IGFBP-2), the GJC response to 30 ng/ml rhIGF-I was 81%, compared with the average of 25%. Finally, as a control, insulin was given in equimolar concentrations. However, GJC was not affected, which suggests that rhIGF-I acted via IGF-I receptors. In summary, the data show that rhIGF-I may increase GJC/ cx43, whereas a higher concentration of rhIGF-I-at which stimulation of proliferation occurred-did not affect GJC/cx43. Furthermore, IGFBP-2 appeared to modulate the action of rhIGF-I on GJC in astrocytes by a paracrine mechanism. (C) 2003 Wiley-Liss, Inc.