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dc.titleUrokinase plasminogen activator mediates changes in human astrocytes modeling fragile X syndrome
dc.contributor.authorPeteri, Ulla-Kaisa
dc.contributor.authorPitkonen, Juho
dc.contributor.authorde Toma, Ilario
dc.contributor.authorNieminen, Otso
dc.contributor.authorUtami, Kagistia Hana
dc.contributor.authorStrandin, Tomas M.
dc.contributor.authorCorcoran, Padraic
dc.contributor.authorRoybon, Laurent
dc.contributor.authorVaheri, Antti
dc.contributor.authorEthell, Iryna
dc.contributor.authorCasarotto, Plinio
dc.contributor.authorPouladi, Mahmoud A.
dc.contributor.authorCastrén, M.L.
dc.identifier.citationPeteri, 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., Castrén, M.L. (2021-08-24). Urokinase plasminogen activator mediates changes in human astrocytes modeling fragile X syndrome. GLIA 69 (12) : 2947-2962. ScholarBank@NUS Repository.
dc.description.abstractThe function of astrocytes intertwines with the extracellular matrix, whose neuron and glial cell-derived components shape neuronal plasticity. Astrocyte abnormalities have been reported 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 compared human FXS and control astrocytes generated from human induced pluripotent stem cells and we found increased expression of urokinase plasminogen activator (uPA), which modulates degradation of extracellular matrix. Several pathways associated with uPA and its receptor function were activated in FXS astrocytes. Levels of uPA were also increased in conditioned medium collected from FXS hiPSC-derived astrocyte cultures and 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 within the docking site for the phospholipase-C?1 (PLC?1), indicating effects of uPA on neuronal plasticity. Gene expression changes during neuronal differentiation preceding astrogenesis likely contributed to properties of astrocytes with FXS-specific alterations that showed specificity by not affecting differentiation of adenosine triphosphate (ATP)-responsive astrocyte population. To conclude, our studies identified uPA as an important regulator of astrocyte function and demonstrated that increased uPA in human FXS astrocytes modulated astrocytic responses and neuronal plasticity. © 2021 The Authors. GLIA published by Wiley Periodicals LLC.
dc.publisherJohn Wiley and Sons Inc
dc.rightsAttribution 4.0 International
dc.sourceScopus OA2021
dc.subjectfragile X syndrome
dc.subjectneuronal plasticity
dc.subjecturokinase plasminogen activator
dc.contributor.departmentDEPT OF PHYSIOLOGY
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