FGF-2 and anosmin-1 are selectively expressed in different types of multiple sclerosis lesions

Multiple sclerosis is a demyelinating disease that affects ~2,000,000 people worldwide. In the advanced stages of the disease, endogenous oligodendrocyte precursors cannot colonize the lesions or differentiate into myelinating oligodendrocytes. During development, both FGF-2 and Anosmin-1 participat...

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Autores: Clemente, Diego, Ortega, M.C., Arenzana, F.J., Castro Soubriet, Fernando de
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/156755
Acceso en línea:http://hdl.handle.net/10261/156755
Access Level:acceso abierto
Palabra clave:FGF-2
Multiple sclerosis
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spelling FGF-2 and anosmin-1 are selectively expressed in different types of multiple sclerosis lesionsClemente, DiegoOrtega, M.C.Arenzana, F.J.Castro Soubriet, Fernando deFGF-2Multiple sclerosisMultiple sclerosis is a demyelinating disease that affects ~2,000,000 people worldwide. In the advanced stages of the disease, endogenous oligodendrocyte precursors cannot colonize the lesions or differentiate into myelinating oligodendrocytes. During development, both FGF-2 and Anosmin-1 participate in oligodendrocyte precursor cell migration, acting via the FGF receptor 1 (FGFR1). Hence, we performed a histopathological and molecular analysis of these developmental modulators in postmortem tissue blocks from multiple sclerosis patients. Accordingly, we demonstrate that the distribution of FGF-2 and Anosmin-1 varies between the different types of multiple sclerosis lesions: FGF-2 is expressed only within active lesions and in the periplaque of chronic lesions, whereas Anosmin-1 is upregulated within chronic lesions and is totally absent in active lesions. We show that the endogenous oligodendrocyte precursor cells recruited toward chronic-active lesions express FGFR1, possibly in response to the FGF-2 produced by microglial cells in the periplaque. Also in human tissue, FGF-2 is upregulated in perivascular astrocytes in regions of the normal-appearing gray matter, where the integrity of the blood-brain barrier is compromised. In culture, FGF-2 and Anosmin-1 influence adult mouse oligodendrocyte precursor cell migration in the same manner as at embryonic stages, providing an explanation for the histopathological observations: FGF-2 attracts/ enhances its migration, which is hindered by Anosmin-1. We propose that FGF-2 and Anosmin-1 are markers for the histopathological type and the level of inflammation of multiple sclerosis lesions, and that they may serve as novel pharmacogenetic targets to design future therapies that favor effective remyelination and protect the blood-brain barrier. © 2011 the authors.Peer ReviewedSociety for NeuroscienceConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2017201720112017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/156755reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1567552026-05-22T06:33:51Z
dc.title.none.fl_str_mv FGF-2 and anosmin-1 are selectively expressed in different types of multiple sclerosis lesions
title FGF-2 and anosmin-1 are selectively expressed in different types of multiple sclerosis lesions
spellingShingle FGF-2 and anosmin-1 are selectively expressed in different types of multiple sclerosis lesions
Clemente, Diego
FGF-2
Multiple sclerosis
title_short FGF-2 and anosmin-1 are selectively expressed in different types of multiple sclerosis lesions
title_full FGF-2 and anosmin-1 are selectively expressed in different types of multiple sclerosis lesions
title_fullStr FGF-2 and anosmin-1 are selectively expressed in different types of multiple sclerosis lesions
title_full_unstemmed FGF-2 and anosmin-1 are selectively expressed in different types of multiple sclerosis lesions
title_sort FGF-2 and anosmin-1 are selectively expressed in different types of multiple sclerosis lesions
dc.creator.none.fl_str_mv Clemente, Diego
Ortega, M.C.
Arenzana, F.J.
Castro Soubriet, Fernando de
author Clemente, Diego
author_facet Clemente, Diego
Ortega, M.C.
Arenzana, F.J.
Castro Soubriet, Fernando de
author_role author
author2 Ortega, M.C.
Arenzana, F.J.
Castro Soubriet, Fernando de
author2_role author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv FGF-2
Multiple sclerosis
topic FGF-2
Multiple sclerosis
description Multiple sclerosis is a demyelinating disease that affects ~2,000,000 people worldwide. In the advanced stages of the disease, endogenous oligodendrocyte precursors cannot colonize the lesions or differentiate into myelinating oligodendrocytes. During development, both FGF-2 and Anosmin-1 participate in oligodendrocyte precursor cell migration, acting via the FGF receptor 1 (FGFR1). Hence, we performed a histopathological and molecular analysis of these developmental modulators in postmortem tissue blocks from multiple sclerosis patients. Accordingly, we demonstrate that the distribution of FGF-2 and Anosmin-1 varies between the different types of multiple sclerosis lesions: FGF-2 is expressed only within active lesions and in the periplaque of chronic lesions, whereas Anosmin-1 is upregulated within chronic lesions and is totally absent in active lesions. We show that the endogenous oligodendrocyte precursor cells recruited toward chronic-active lesions express FGFR1, possibly in response to the FGF-2 produced by microglial cells in the periplaque. Also in human tissue, FGF-2 is upregulated in perivascular astrocytes in regions of the normal-appearing gray matter, where the integrity of the blood-brain barrier is compromised. In culture, FGF-2 and Anosmin-1 influence adult mouse oligodendrocyte precursor cell migration in the same manner as at embryonic stages, providing an explanation for the histopathological observations: FGF-2 attracts/ enhances its migration, which is hindered by Anosmin-1. We propose that FGF-2 and Anosmin-1 are markers for the histopathological type and the level of inflammation of multiple sclerosis lesions, and that they may serve as novel pharmacogenetic targets to design future therapies that favor effective remyelination and protect the blood-brain barrier. © 2011 the authors.
publishDate 2011
dc.date.none.fl_str_mv 2011
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/156755
url http://hdl.handle.net/10261/156755
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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