Long non-coding RNA MALAT1 regulates retinal neurodegeneration through CREB signaling.
Long non-coding RNA MALAT1 regulates retinal neurodegeneration through CREB signaling.
复制标题
长非编码RNA MALAT1通过CREB信号传导调节视网膜神经变性
DOI：
10.15252/emmm.201505725
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发表时间：
2016-04-01
影响因子：
11.1
通讯作者：
Yan B
中科院分区：
文献类型：
--
作者：
Yao J;Wang XQ;Li YJ;Shan K;Yang H;Wang YN;Yao MD;Liu C;Li XM;Shen Y;Liu JY;Cheng H;Yuan J;Zhang YY;Jiang Q;Yan B
神经和血管系统，虽然功能不同，但有许多共同的功能维持调节器。长链非编码RNA（lncRNA）是许多生物过程和人类疾病中的重要参与者。我们以前确定了MALAT 1在微血管功能障碍中的作用。然而，它在神经变性中的作用仍然未知。在这里，我们使用眼睛作为模型来研究MALAT 1在视网膜神经变性中的作用。我们发现MALAT 1表达在应激时在视网膜、Müller细胞和原代视网膜神经节细胞（RGC）中显著上调。MALAT 1基因敲减减少了体内和体外反应性胶质增生、Müller细胞活化和RGC存活。MALAT 1-CREB结合通过抑制PP 2A介导的去磷酸化来维持CREB磷酸化，从而导致CREB信号持续激活。临床和动物实验表明，MALAT 1功能障碍与神经退行性过程和几种人类疾病有关。总的来说，这项研究表明，MALAT 1可能通过CREB信号调节视网膜神经变性的发展。
The nervous and vascular systems, although functionally different, share many common regulators of function maintenance. Long non‐coding RNAs (lncRNAs) are important players in many biological processes and human disorders. We previously identified a role of MALAT1 in microvascular dysfunction. However, its role in neurodegeneration is still unknown. Here, we used the eye as the model to investigate the role of MALAT1 in retinal neurodegeneration. We show that MALAT1 expression is significantly up‐regulated in the retinas, Müller cells, and primary retinal ganglion cells (RGCs) upon stress. MALAT1 knockdown reduces reactive gliosis, Müller cell activation, and RGC survival in vivo and in vitro. MALAT1‐CREB binding maintains CREB phosphorylation by inhibiting PP2A‐mediated dephosphorylation, which leads to continuous CREB signaling activation. Clinical and animal experimentation suggests that MALAT1 dysfunction is implicated in neurodegenerative processes and several human disorders. Collectively, this study reveals that MALAT1 might regulate the development of retinal neurodegeneration through CREB signaling.