Long non‐coding RNA MALAT1 regulates retinal neurodegeneration through CREB signaling
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. Howe...
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Published in | EMBO molecular medicine Vol. 8; no. 4; pp. 346 - 362 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.04.2016
EMBO Press John Wiley and Sons Inc Springer Nature |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
Synopsis
Long non‐coding RNA MALAT1 knockdown decreases retinal reactive gliosis, Müller cell activation, and RGC survival via interactions with CREB signaling.
MALAT1 expression is up‐regulated in retinas, Müller cells, and primary retinal ganglion cells (RGCs) under stress.
MALAT1 knockdown decreases reactive gliosis, Müller cell activation, and RGC survival
in vivo
and
in vitro
.
MALAT1 interacts with the CREB signaling pathway to regulate Müller cell and RGC function.
MALAT1 dysregulation is implicated in several human neurological diseases.
Graphical Abstract
Long non‐coding RNA MALAT1 knockdown decreases retinal reactive gliosis, Müller cell activation, and RGC survival via interactions with CREB signaling. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work |
ISSN: | 1757-4676 1757-4684 1757-4684 |
DOI: | 10.15252/emmm.201505725 |