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https://hdl.handle.net/10216/120739
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DC Field | Value | Language |
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dc.creator | Rocha, DN | - |
dc.creator | Ferraz-Nogueira, JP | - |
dc.creator | Barrias, CC | - |
dc.creator | Relvas, JB | - |
dc.creator | Pêgo, AP | - |
dc.date.accessioned | 2019-06-25T12:08:41Z | - |
dc.date.available | 2019-06-25T12:08:41Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 1662-5102 | - |
dc.identifier.uri | https://hdl.handle.net/10216/120739 | - |
dc.description.abstract | Glial scars are widely seen as a (bio)mechanical barrier to central nervous system regeneration. Due to the lack of a screening platform, which could allow in-vitro testing of several variables simultaneously, up to now no comprehensive study has addressed and clarified how different lesion microenvironment properties affect astrogliosis. Using astrocytes cultured in alginate gels and meningeal fibroblast conditioned medium, we have built a simple and reproducible 3D culture system of astrogliosis mimicking many features of the glial scar. Cells in this 3D culture model behave similarly to scar astrocytes, showing changes in gene expression (e.g., GFAP) and increased extra-cellular matrix production (chondroitin 4 sulfate and collagen), inhibiting neuronal outgrowth. This behavior being influenced by the hydrogel network properties. Astrocytic reactivity was found to be dependent on RhoA activity, and targeting RhoA using shRNA-mediated lentivirus reduced astrocytic reactivity. Further, we have shown that chemical inhibition of RhoA with ibuprofen or indirectly targeting RhoA by the induction of extracellular matrix composition modification with chondroitinase ABC, can diminish astrogliosis. Besides presenting the extracellular matrix as a key modulator of astrogliosis, this simple, controlled and reproducible 3D culture system constitutes a good scar-like system and offers great potential in future neurodegenerative mechanism studies, as well as in drug screenings envisaging the development of new therapeutic approaches to minimize the effects of the glial scar in the context of central nervous system disease. | - |
dc.description.sponsorship | This work had the financial support of the Portuguese Fundação para a Ciência e Tecnologia (FCT) / Ministério da Educação e Ciência (MEC) through National Funds and, when applicable, co-financed by the FEDER via the PT2020 Partnership Agreement under the 4293 Unit I&D. DR acknowledges FCT for her PhD scholarship /SFRH/BD/64079/2009). Authors thank Dr. Michiyuki Matsuda (Kyoto University, Japan) for the RhoA FRET probe with enhanced sensitivity and Dr. Yingxiao Wang (University of California, USA) for the Src FRET probe. | - |
dc.language.iso | eng | - |
dc.publisher | Frontiers Research Foundation | - |
dc.relation | info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F64079%2F2009/PT | - |
dc.relation.ispartof | Frontiers in Cellular Neuroscience, vol. 9:377 | - |
dc.rights | openAccess | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.subject | Astrocytes | - |
dc.subject | Astrogliosis | - |
dc.subject | Extracellular matrix | - |
dc.subject | Mechanical properties | - |
dc.subject | Mechanotransduction | - |
dc.subject | RhoA | - |
dc.title | Extracellular environment contribution to astrogliosis-lessons learned from a tissue engineered 3D model of the glial scar | - |
dc.type | Artigo em Revista Científica Internacional | - |
dc.contributor.uporto | Instituto de Investigação e Inovação em Saúde | - |
dc.identifier.doi | 10.3389/fncel.2015.00377 | - |
dc.relation.publisherversion | https://www.frontiersin.org/articles/10.3389/fncel.2015.00377/full | - |
Appears in Collections: | I3S - Artigo em Revista Científica Internacional |
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fncel201500377.pdf | 1.98 MB | Adobe PDF | View/Open |
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