Neuropeptide Y-evoked proliferation of retinal glial (Muller) cells
Neuropeptide Y-evoked proliferation of retinal glial (Muller) cells
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DOI：
10.1007/s00417-004-0954-3
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发表时间：
2004-11-01
影响因子：
2.7
通讯作者：
Bringmann, A
中科院分区：
文献类型：
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作者：
Milenkovic, I;Weick, M;Bringmann, A
背景：增生性玻璃体视网膜病变(PVR)患者视网膜和纤维细胞膜中的胶质细胞被描述为上调神经肽Y(NPY)的Y-1受体的表达(Soler等人：Glia 39：320,2002)。然而，Y-1受体的激活是否会导致视网膜神经胶质细胞的增殖尚不清楚。我们研究了NPY是否对视网膜神经胶质细胞具有增殖刺激作用，并比较了NPY诱导的信号转导和嘌呤能P2Y受体信号转导。方法：用溴脱氧尿嘧啶核苷对原代培养的豚鼠Muller神经胶质细胞进行增殖实验，分别用Y-1受体阻断剂、酪氨酸激酶受体阻断剂(RTKs)、丝裂原活化蛋白激酶(MAPKs)阻断剂和磷脂酰肌醇-3K(PI3K)阻断剂。结果：NPY对Muller细胞的增殖具有双相作用。低浓度(0.1 ng/m l和1 ng/m l)降低细胞增殖率，高浓度(100 ng/m l)则促进Muller细胞增殖。刺激Y-1受体、激活p44/p42MAPK和部分激活p38MAPK介导了NPY诱导的细胞增殖。此外，Y-1受体诱导的PI3K的激活以及血小板来源的RTK和表皮生长因子RTK的反式激活是NPY充分有丝分裂的必要条件。Y-1和P2Y受体在Muller细胞中共享部分共同的信号转导通路。结论：在PVR过程中，NPY大量释放到受损视网膜，可能参与刺激视网膜神经胶质细胞的增殖。
Background: Glial cells in human retinas and in fibrocellular membranes from patients with proliferative vitreoretinopathy (PVR) have been described to upregulate their expression of Y-1 receptors for neuropeptide Y (NPY) (Soler et al.: Glia 39:320, 2002). However, it is unknown whether Y-1 receptor activation causes proliferation of retinal glial cells. We investigated whether NPY exerts a proliferation-stimulating effect on retinal glial cells, and compared the NPY-evoked signaling with the signaling of purinergic P2Y receptors. Methods: Proliferation assays using bromodeoxyuridine were carried out on primarily cultured Muller glial cells of the guinea pig, in the absence and presence of blockers of Y-1 receptors, of receptor tyrosine kinases (RTKs), of mitogen-activated protein kinases (MAPKs) and of phosphatidylinositol-3 kinase (PI3K). Results: NPY exerted a biphasic effect on Muller cell proliferation. At low concentrations (0.1 ng/ml and 1 ng/ml) it decreased the proliferation rate of the cells, while at higher concentration (100 ng/ml) it increased Muller cell proliferation. The NPY-evoked proliferation was mediated by Y-1 receptor stimulation and by activation of the p44/p42 MAPKs and partially of the p38 MAPK. Moreover, Y-1 receptor-induced activation of PI3K as well as transactivations of the platelet-derived and the epidermal growth factor RTKs were necessary for full mitogenic effect of NPY. Y-1 and P2Y receptors share partially common signal transduction pathways in Muller cells. Conclusion: It is suggested that NPY may be involved in stimulation of retinal glial cell proliferation during PVR when it is released at higher amounts into the injured retina.