Endothelin2 Induces Expression of Genes Associated with Reactive Gliosis in Retinal Müller Cells.
Endothelin2 Induces Expression of Genes Associated with Reactive Gliosis in Retinal Müller Cells.
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DOI：
10.3109/02713683.2014.982828
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发表时间：
2015
影响因子：
2
通讯作者：
Dudley VJ
中科院分区：
文献类型：
--
作者：
Sarthy VP;Sawkar H;Dudley VJ
光感受器变性通常伴随着米勒（神经胶质）细胞的反应性神经胶质增生和基因表达变化。在穆勒细胞中诱导这些变化的信号通路尚不清楚。有人提出，退化光感受器释放的内皮素 2 (EDN2) 可能会诱导 Müller 细胞发生胶质细胞变化。在本研究中，我们通过确定用 EDN2 处理 Müller 细胞培养物是否会导致已知在体内活化的 Müller 细胞中表达的基因上调来直接检验该假设。使用已建立的大鼠 Müller 细胞系 (rMC-1) 进行实验，并通过 qRT-PCR 评估基因表达。我们观察到 EDN2 治疗上调了胶质纤维酸性蛋白 (Gfap)、Serpina3n 和内皮素受体 B (EdnrB) 的转录本，这三个基因与 Müller 细胞中反应性神经胶质增生相关。睫状神经营养因子（CNTF）治疗同样导致 Gfap、Serpina3n 和 EdnrB 转录物的诱导，而谷氨酸治疗没有显着效果。这一发现支持 EDN2 作为光感受器和穆勒细胞之间信号传导剂的作用。
Photoreceptor degeneration is normally accompanied by reactive gliosis and gene expression changes in Müller (glial) cells. The signaling pathway involved inducing these changes in Müller cells is not known. It has been proposed that endothelin2 (EDN2) released by degenerating photoreceptors might induce gliotic changes in Müller cells. In the present study, we directly tested the hypothesis by determining whether treatment of Müller cell cultures with EDN2 results in upregulation of genes known to be expressed in activated Müller cells in vivo. Experiments were carried using an established rat Müller cell line (rMC-1), and gene expression was assessed by qRT-PCR. We observed that EDN2 treatment upregulated transcripts for glial fibrillary acidic protein (Gfap), Serpina3n and endothelin receptor B (EdnrB), three genes associated with reactive gliosis in Müller cells. Ciliary neurotrophic factor (CNTF) treatment similarly led to induction of Gfap, Serpina3n and EdnrB transcripts, whereas glutamate treatment had no significant effect. The finding supports a role for EDN2 as a signaling agent between photoreceptors and Müller cells.