Urokinase plasminogen activator mediates changes in human astrocytes modeling fragile X syndrome

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Peteri , U-K , Pitkonen , J , de Toma , I , Nieminen , O , Utami , K H , Strandin , T M , Corcoran , P , Roybon , L , Vaheri , A , Ethell , I , Casarotto , P , Pouladi , M A & Castren , M L 2021 , ' Urokinase plasminogen activator mediates changes in human astrocytes modeling fragile X syndrome ' , Glia , vol. 69 , no. 12 , pp. 2947-2962 . https://doi.org/10.1002/glia.24080

Title: Urokinase plasminogen activator mediates changes in human astrocytes modeling fragile X syndrome
Author: Peteri, Ulla-Kaisa; Pitkonen, Juho; de Toma, Ilario; Nieminen, Otso; Utami, Kagistia Hana; Strandin, Tomas M.; Corcoran, Padraic; Roybon, Laurent; Vaheri, Antti; Ethell, Iryna; Casarotto, Plinio; Pouladi, Mahmoud A.; Castren, Maija L.
Contributor organization: NeuroDevDiseaseModelling
Medicum
Department of Physiology
Department of Virology
Viral Zoonosis Research Unit
Date: 2021-12
Language: eng
Number of pages: 16
Belongs to series: Glia
ISSN: 0894-1491
DOI: https://doi.org/10.1002/glia.24080
URI: http://hdl.handle.net/10138/340524
Abstract: Astrocyte function intertwines with the extracellular matrix, whose glial cell-derived components shape neuronal plasticity. Astrocyte abnormalities are found in the brain of the mouse model for fragile X syndrome (FXS), the most common cause of inherited intellectual disability, and a monogenic cause of autism spectrum disorder. We generated human induced pluripotent stem cell-derived FXS and control astrocytes and we found that several pathways associated with urokinase plasminogen activator (uPA) that modulates degradation of extracellular matrix were activated in FXS astrocytes compared with controls. Expression of uPA was increased in FXS astrocytes and levels of uPA were also increased in conditioned medium collected from FXS astrocyte cultures. Levels of uPA correlated inversely with intracellular Ca2+ responses to activation of L-type voltage-gated calcium channels in human astrocytes. Increased uPA augmented neuronal phosphorylation of TrkB, indicating effects of uPA on neuronal plasticity. FXS-specific changes of gene expression during neuronal differentiation preceding astrogenesis likely contributed to altered properties of FXS astrocytes. Our results identified uPA as an important regulator of astrocyte function and demonstrated that increased uPA in human FXS astrocytes modulated astrocytic responses and neuronal plasticity.
Subject: astrocyte
fragile X syndrome
neuronal plasticity
urokinase plasminogen activator
CENTRAL-NERVOUS-SYSTEM
WNT/BETA-CATENIN
MOUSE MODEL
RECEPTOR
DIFFERENTIATION
MIGRATION
RESPONSES
EPILEPSY
PATHWAY
GENE
3112 Neurosciences
3124 Neurology and psychiatry
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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