Astrocytic heterogeneous nuclear ribonucleoprotein U is involved in scar formation after spinal cord injury

Abstract Astrocytes have a beneficial role in tissue repair after central nervous system (CNS) injury. Although astrocyte proliferation is activated in response to injury, the intracellular mechanisms of astrocyte proliferation during acute phase of injury are not fully clarified. In this study, by...

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Main Authors: Lili Quan, Akiko Uyeda, Ichiro Manabe, Rieko Muramatsu
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Journal of Neuroinflammation
Subjects:
Online Access:https://doi.org/10.1186/s12974-025-03351-4
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author Lili Quan
Akiko Uyeda
Ichiro Manabe
Rieko Muramatsu
author_facet Lili Quan
Akiko Uyeda
Ichiro Manabe
Rieko Muramatsu
author_sort Lili Quan
collection DOAJ
description Abstract Astrocytes have a beneficial role in tissue repair after central nervous system (CNS) injury. Although astrocyte proliferation is activated in response to injury, the intracellular mechanisms of astrocyte proliferation during acute phase of injury are not fully clarified. In this study, by functionally screening the highly expressed genes in the pathological state of spinal astrocytes, heterogeneous nuclear ribonucleoprotein U (Hnrnpu) is identified as a potential endogenous molecule that regulates astrocyte proliferation and the following scar formation. Inhibition of Hnrnpu in astrocytes impairs the formation of astrocytic glial scar, motor function recovery, and neuronal regeneration after spinal cord injury (SCI) in mice. In human astrocytes, HNRNPU knockdown downregulates the genes related to the astrocyte functions in scar formation and neuronal regeneration. These findings uncover that modulation of endogenous astrocytic function would be a promising therapeutic avenue to restore neurological function after CNS injury.
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institution Kabale University
issn 1742-2094
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publishDate 2025-01-01
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series Journal of Neuroinflammation
spelling doaj-art-9ee1a97dc67c45708268114a51766d652025-02-02T12:35:00ZengBMCJournal of Neuroinflammation1742-20942025-01-0122111610.1186/s12974-025-03351-4Astrocytic heterogeneous nuclear ribonucleoprotein U is involved in scar formation after spinal cord injuryLili Quan0Akiko Uyeda1Ichiro Manabe2Rieko Muramatsu3Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and PsychiatryDepartment of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and PsychiatryDepartment of Systems Medicine, Graduate School of Medicine, Chiba UniversityDepartment of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and PsychiatryAbstract Astrocytes have a beneficial role in tissue repair after central nervous system (CNS) injury. Although astrocyte proliferation is activated in response to injury, the intracellular mechanisms of astrocyte proliferation during acute phase of injury are not fully clarified. In this study, by functionally screening the highly expressed genes in the pathological state of spinal astrocytes, heterogeneous nuclear ribonucleoprotein U (Hnrnpu) is identified as a potential endogenous molecule that regulates astrocyte proliferation and the following scar formation. Inhibition of Hnrnpu in astrocytes impairs the formation of astrocytic glial scar, motor function recovery, and neuronal regeneration after spinal cord injury (SCI) in mice. In human astrocytes, HNRNPU knockdown downregulates the genes related to the astrocyte functions in scar formation and neuronal regeneration. These findings uncover that modulation of endogenous astrocytic function would be a promising therapeutic avenue to restore neurological function after CNS injury.https://doi.org/10.1186/s12974-025-03351-4AstrocytesSpinal cord injuryGlial scar formationRegeneration
spellingShingle Lili Quan
Akiko Uyeda
Ichiro Manabe
Rieko Muramatsu
Astrocytic heterogeneous nuclear ribonucleoprotein U is involved in scar formation after spinal cord injury
Journal of Neuroinflammation
Astrocytes
Spinal cord injury
Glial scar formation
Regeneration
title Astrocytic heterogeneous nuclear ribonucleoprotein U is involved in scar formation after spinal cord injury
title_full Astrocytic heterogeneous nuclear ribonucleoprotein U is involved in scar formation after spinal cord injury
title_fullStr Astrocytic heterogeneous nuclear ribonucleoprotein U is involved in scar formation after spinal cord injury
title_full_unstemmed Astrocytic heterogeneous nuclear ribonucleoprotein U is involved in scar formation after spinal cord injury
title_short Astrocytic heterogeneous nuclear ribonucleoprotein U is involved in scar formation after spinal cord injury
title_sort astrocytic heterogeneous nuclear ribonucleoprotein u is involved in scar formation after spinal cord injury
topic Astrocytes
Spinal cord injury
Glial scar formation
Regeneration
url https://doi.org/10.1186/s12974-025-03351-4
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AT akikouyeda astrocyticheterogeneousnuclearribonucleoproteinuisinvolvedinscarformationafterspinalcordinjury
AT ichiromanabe astrocyticheterogeneousnuclearribonucleoproteinuisinvolvedinscarformationafterspinalcordinjury
AT riekomuramatsu astrocyticheterogeneousnuclearribonucleoproteinuisinvolvedinscarformationafterspinalcordinjury