Retinal Degeneration Triggers the Activation of YAP/TEAD in Reactive Müller Cells.
Retinal Degeneration Triggers the Activation of YAP/TEAD in Reactive Müller Cells.
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DOI：
10.1167/iovs.16-21366
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发表时间：
2017-04-01
影响因子：
4.4
通讯作者：
Perron M
中科院分区：
文献类型：
--
作者：
Hamon A;Masson C;Bitard J;Gieser L;Roger JE;Perron M
在视网膜变性过程中，<s:1> ller胶质细胞通过反应性胶质增生对光感受器丧失作出反应，其影响既有有害的，也有有益的。因此，增加我们对<s:1>勒细胞对视网膜变性的复杂分子反应的了解对于开发新的治疗策略至关重要。这项工作的目的是确定新的因素参与<s:1>勒细胞对光感受器细胞死亡的反应。在P30时对野生型和退化的rd10小鼠视网膜进行全转录组测序。采用定量RT-PCR （RT-qPCR）方法评估几种差异表达基因的mRNA丰度变化。western blot和免疫组化分别检测蛋白表达水平和视网膜细胞定位。来自全转录组学数据的通路水平分析显示，Hippo/YAP通路是rd10视网膜光感受器变性反应中改变的主要信号通路之一。我们发现该通路的下游效应物YAP和TEAD1在m<s:1> ller细胞中特异性表达，并且在光感受器变性发生后，它们在rd10反应性m<s:1> ller胶质细胞中的mRNA和蛋白水平表达均增加。YAP/TEAD复合体的两个转录靶基因Ctgf和Cyr61的表达也在光感受器缺失后上调。这项工作首次揭示了Hippo通路的关键下游效应物YAP和TEAD1在<s:1> ller细胞中特异性表达。我们还发现在病理条件下，反应性<s:1> ller细胞中Hippo/YAP通路组分的表达和活性出现了异常。
During retinal degeneration, Müller glia cells respond to photoreceptor loss by undergoing reactive gliosis, with both detrimental and beneficial effects. Increasing our knowledge of the complex molecular response of Müller cells to retinal degeneration is thus essential for the development of new therapeutic strategies. The purpose of this work was to identify new factors involved in Müller cell response to photoreceptor cell death. Whole transcriptome sequencing was performed from wild-type and degenerating rd10 mouse retinas at P30. The changes in mRNA abundance for several differentially expressed genes were assessed by quantitative RT-PCR (RT-qPCR). Protein expression level and retinal cellular localization were determined by western blot and immunohistochemistry, respectively. Pathway-level analysis from whole transcriptomic data revealed the Hippo/YAP pathway as one of the main signaling pathways altered in response to photoreceptor degeneration in rd10 retinas. We found that downstream effectors of this pathway, YAP and TEAD1, are specifically expressed in Müller cells and that their expression, at both the mRNA and protein levels, is increased in rd10 reactive Müller glia after the onset of photoreceptor degeneration. The expression of Ctgf and Cyr61, two target genes of the transcriptional YAP/TEAD complex, is also upregulated following photoreceptor loss. This work reveals for the first time that YAP and TEAD1, key downstream effectors of the Hippo pathway, are specifically expressed in Müller cells. We also uncovered a deregulation of the expression and activity of Hippo/YAP pathway components in reactive Müller cells under pathologic conditions.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
5.1
作者：
Fischer, Andy J.;Bongini, Rachel
通讯作者：
Bongini, Rachel
N-甲基-N-亚硝基脲诱导小鼠视网膜变性
影响因子：
3.4
作者：
Chen, Yuan-Yuan;Liu, Shi-Liang;Shen, Yin
通讯作者：
Shen, Yin
影响因子：
64.8
作者：
Gregorieff, Alex;Liu, Yu;Wrana, Jeffrey L.
通讯作者：
Wrana, Jeffrey L.
影响因子：
12.4
作者：
Di Cara, F.;Maile, T. M.;King-Jones, K.
通讯作者：
King-Jones, K.