Ciliary neurotrophic factor induces genes associated with inflammation and gliosis in the retina: a gene profiling study of flow-sorted, Müller cells.
Ciliary neurotrophic factor induces genes associated with inflammation and gliosis in the retina: a gene profiling study of flow-sorted, Müller cells.
复制标题
DOI：
10.1371/journal.pone.0020326
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Sarthy VP
中科院分区：
文献类型：
--
作者：
Xue W;Cojocaru RI;Dudley VJ;Brooks M;Swaroop A;Sarthy VP
睫状神经营养因子（Ciliary neurotrophic factor， CNTF）是白细胞介素-6细胞因子家族的一员，参与视网膜神经元的发育、分化和存活。CNTF的作用机制及其在视网膜中的细胞靶标尚不清楚。据推测，CNTF的一些生物学效应是通过视网膜胶质细胞介导的；然而，CNTF诱导的视网膜胶质细胞的分子变化尚未被阐明。因此，我们在体内检测了暴露于CNTF的纯化m<s:1>神经胶质细胞的基因表达动力学。在玻璃体内注射CNTF后1天或3天，从mgmap -egfp转基因小鼠中流式分选细胞。使用纯化的m<s:1> ller细胞的RNA进行微阵列分析显示，在CNTF的作用下，近1000个转录本的差异表达发生了2到17倍的变化。在CNTF处理后1天或3天对m<s:1> ller细胞的转录谱进行比较，结果显示转录基因数量增加，表达模式发生变化。匠心途径分析显示，这些差异调节基因属于不同的功能类型，如细胞因子、生长因子、g蛋白偶联受体、转运体和离子通道。有趣的是，CNTF诱导的许多基因也在遗传性或实验性视网膜变性小鼠的反应性m<s:1> ller细胞中高度表达。基因谱的进一步分析显示，在<s:1> ller细胞、星形胶质细胞和RPE之间，转录模式有20-30%的重叠。我们的研究为<s:1>状神经胶质细胞在介导细胞因子反应中的生物学功能提供了新的分子见解。我们认为CNTF重塑了<s:1> ller细胞的基因表达谱，从而诱导了与转录、细胞周期调节和炎症反应相关的网络。CNTF似乎也是视网膜胶质细胞形成的诱导剂。
Ciliary neurotrophic factor (CNTF), a member of the interleukin-6 cytokine family, has been implicated in the development, differentiation and survival of retinal neurons. The mechanisms of CNTF action as well as its cellular targets in the retina are poorly understood. It has been postulated that some of the biological effects of CNTF are mediated through its action via retinal glial cells; however, molecular changes in retinal glia induced by CNTF have not been elucidated. We have, therefore, examined gene expression dynamics of purified Müller (glial) cells exposed to CNTF in vivo. Müller cells were flow-sorted from mgfap-egfp transgenic mice one or three days after intravitreal injection of CNTF. Microarray analysis using RNA from purified Müller cells showed differential expression of almost 1,000 transcripts with two- to seventeen-fold change in response to CNTF. A comparison of transcriptional profiles from Müller cells at one or three days after CNTF treatment showed an increase in the number of transcribed genes as well as a change in the expression pattern. Ingenuity Pathway Analysis showed that the differentially regulated genes belong to distinct functional types such as cytokines, growth factors, G-protein coupled receptors, transporters and ion channels. Interestingly, many genes induced by CNTF were also highly expressed in reactive Müller cells from mice with inherited or experimentally induced retinal degeneration. Further analysis of gene profiles revealed 20–30% overlap in the transcription pattern among Müller cells, astrocytes and the RPE. Our studies provide novel molecular insights into biological functions of Müller glial cells in mediating cytokine response. We suggest that CNTF remodels the gene expression profile of Müller cells leading to induction of networks associated with transcription, cell cycle regulation and inflammatory response. CNTF also appears to function as an inducer of gliosis in the retina.
登录
查看更多内容
DOI：
10.1073/pnas.95.7.3978
发表时间：
1998-03-31
影响因子：
11.1
作者：
Di Polo, A;Aigner, LJ;Aguayo, AJ
通讯作者：
Aguayo, AJ
影响因子：
4.4
作者：
Bai, Yujing;Shi, ZhiHua;Saragovi, H. Uri
通讯作者：
Saragovi, H. Uri
影响因子：
3.4
作者：
Bok, D;Yasumura, D;Lavail, MM
通讯作者：
Lavail, MM
影响因子：
3.5
作者：
Alonzi, T;Middleton, G;Davies, AM
通讯作者：
Davies, AM
影响因子：
1.7
作者：
Cui, Q;Harvey, AR
通讯作者：
Harvey, AR