Galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function

Galectins control critical pathophysiological processes, including the progression and resolution of central nervous system (CNS) inflammation. In spite of considerable progress in dissecting their role within lymphoid organs, their functions within the inflamed CNS remain elusive. Here, we investig...

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Autores principales: Pasquini, L.A., Millet, V., Hoyos, H.C., Giannoni, J.P., Croci, D.O., Marder, M., Liu, F.T., Rabinovich, G.A., Pasquini, J.M.
Formato: Artículo publishedVersion
Lenguaje:Inglés
Publicado: 2011
Materias:
rat
Mus
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_13509047_v18_n11_p1746_Pasquini
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spelling paperaa:paper_13509047_v18_n11_p1746_Pasquini2023-06-12T16:49:50Z Galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function Cell Death Differ. 2011;18(11):1746-1756 Pasquini, L.A. Millet, V. Hoyos, H.C. Giannoni, J.P. Croci, D.O. Marder, M. Liu, F.T. Rabinovich, G.A. Pasquini, J.M. differentiation galectin-3 galectins myelination oligodendrocyte galectin 1 galectin 3 gelatinase A gelatinase B glycan myelin animal cell animal experiment animal model animal tissue anxiety disorder article astrocyte cell differentiation controlled study corpus callosum corpus striatum demyelination enzyme activity glycosylation microglia mouse nerve fiber nonhuman oligodendroglia priority journal protein expression protein function rat upregulation wild type Animals Astrocytes Axons Behavior, Animal Cell Differentiation Cells, Cultured Cuprizone Galectin 1 Galectin 3 Mice Mice, Inbred C57BL Microglia Myelin Sheath Oligodendroglia Polysaccharides Promoter Regions, Genetic Protein Binding Rats Rats, Wistar Mus Galectins control critical pathophysiological processes, including the progression and resolution of central nervous system (CNS) inflammation. In spite of considerable progress in dissecting their role within lymphoid organs, their functions within the inflamed CNS remain elusive. Here, we investigated the role of galectin-glycan interactions in the control of oligodendrocyte (OLG) differentiation, myelin integrity and function. Both galectin-1 and-3 were abundant in astrocytes and microglia. Although galectin-1 was abundant in immature but not in differentiated OLGs, galectin-3 was upregulated during OLG differentiation. Biochemical analysis revealed increased activity of metalloproteinases responsible for cleaving galectin-3 during OLG differentiation and modulating its biological activity. Exposure to galectin-3 promoted OLG differentiation in a dose-and carbohydrate-dependent fashion consistent with the glycosylation signature of immature versus differentiated OLG. Accordingly, conditioned media from galectin-3-expressing, but not galectin-3-deficient (Lgals3/) microglia, successfully promoted OLG differentiation. Supporting these findings, morphometric analysis showed a significant decrease in the frequency of myelinated axons, myelin turns (lamellae) and g-ratio in the corpus callosum and striatum of Lgals3/compared with wild-type (WT) mice. Moreover, the myelin structure was loosely wrapped around the axons and less smooth in Lgals3/mice versus WT mice. Behavior analysis revealed decreased anxiety in Lgals3/mice similar to that observed during early demyelination induced by cuprizone intoxication. Finally, commitment toward the oligodendroglial fate was favored in neurospheres isolated from WT but not Lgals3/mice. Hence, glial-derived galectin-3, but not galectin-1, promotes OLG differentiation, thus contributing to myelin integrity and function with critical implications in the recovery of inflammatory demyelinating disorders. © 2011 Macmillan Publishers Limited All rights reserved. Fil:Croci, D.O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2011 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_13509047_v18_n11_p1746_Pasquini
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language Inglés
orig_language_str_mv eng
topic differentiation
galectin-3
galectins
myelination
oligodendrocyte
galectin 1
galectin 3
gelatinase A
gelatinase B
glycan
myelin
animal cell
animal experiment
animal model
animal tissue
anxiety disorder
article
astrocyte
cell differentiation
controlled study
corpus callosum
corpus striatum
demyelination
enzyme activity
glycosylation
microglia
mouse
nerve fiber
nonhuman
oligodendroglia
priority journal
protein expression
protein function
rat
upregulation
wild type
Animals
Astrocytes
Axons
Behavior, Animal
Cell Differentiation
Cells, Cultured
Cuprizone
Galectin 1
Galectin 3
Mice
Mice, Inbred C57BL
Microglia
Myelin Sheath
Oligodendroglia
Polysaccharides
Promoter Regions, Genetic
Protein Binding
Rats
Rats, Wistar
Mus
spellingShingle differentiation
galectin-3
galectins
myelination
oligodendrocyte
galectin 1
galectin 3
gelatinase A
gelatinase B
glycan
myelin
animal cell
animal experiment
animal model
animal tissue
anxiety disorder
article
astrocyte
cell differentiation
controlled study
corpus callosum
corpus striatum
demyelination
enzyme activity
glycosylation
microglia
mouse
nerve fiber
nonhuman
oligodendroglia
priority journal
protein expression
protein function
rat
upregulation
wild type
Animals
Astrocytes
Axons
Behavior, Animal
Cell Differentiation
Cells, Cultured
Cuprizone
Galectin 1
Galectin 3
Mice
Mice, Inbred C57BL
Microglia
Myelin Sheath
Oligodendroglia
Polysaccharides
Promoter Regions, Genetic
Protein Binding
Rats
Rats, Wistar
Mus
Pasquini, L.A.
Millet, V.
Hoyos, H.C.
Giannoni, J.P.
Croci, D.O.
Marder, M.
Liu, F.T.
Rabinovich, G.A.
Pasquini, J.M.
Galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function
topic_facet differentiation
galectin-3
galectins
myelination
oligodendrocyte
galectin 1
galectin 3
gelatinase A
gelatinase B
glycan
myelin
animal cell
animal experiment
animal model
animal tissue
anxiety disorder
article
astrocyte
cell differentiation
controlled study
corpus callosum
corpus striatum
demyelination
enzyme activity
glycosylation
microglia
mouse
nerve fiber
nonhuman
oligodendroglia
priority journal
protein expression
protein function
rat
upregulation
wild type
Animals
Astrocytes
Axons
Behavior, Animal
Cell Differentiation
Cells, Cultured
Cuprizone
Galectin 1
Galectin 3
Mice
Mice, Inbred C57BL
Microglia
Myelin Sheath
Oligodendroglia
Polysaccharides
Promoter Regions, Genetic
Protein Binding
Rats
Rats, Wistar
Mus
description Galectins control critical pathophysiological processes, including the progression and resolution of central nervous system (CNS) inflammation. In spite of considerable progress in dissecting their role within lymphoid organs, their functions within the inflamed CNS remain elusive. Here, we investigated the role of galectin-glycan interactions in the control of oligodendrocyte (OLG) differentiation, myelin integrity and function. Both galectin-1 and-3 were abundant in astrocytes and microglia. Although galectin-1 was abundant in immature but not in differentiated OLGs, galectin-3 was upregulated during OLG differentiation. Biochemical analysis revealed increased activity of metalloproteinases responsible for cleaving galectin-3 during OLG differentiation and modulating its biological activity. Exposure to galectin-3 promoted OLG differentiation in a dose-and carbohydrate-dependent fashion consistent with the glycosylation signature of immature versus differentiated OLG. Accordingly, conditioned media from galectin-3-expressing, but not galectin-3-deficient (Lgals3/) microglia, successfully promoted OLG differentiation. Supporting these findings, morphometric analysis showed a significant decrease in the frequency of myelinated axons, myelin turns (lamellae) and g-ratio in the corpus callosum and striatum of Lgals3/compared with wild-type (WT) mice. Moreover, the myelin structure was loosely wrapped around the axons and less smooth in Lgals3/mice versus WT mice. Behavior analysis revealed decreased anxiety in Lgals3/mice similar to that observed during early demyelination induced by cuprizone intoxication. Finally, commitment toward the oligodendroglial fate was favored in neurospheres isolated from WT but not Lgals3/mice. Hence, glial-derived galectin-3, but not galectin-1, promotes OLG differentiation, thus contributing to myelin integrity and function with critical implications in the recovery of inflammatory demyelinating disorders. © 2011 Macmillan Publishers Limited All rights reserved.
format Artículo
Artículo
publishedVersion
author Pasquini, L.A.
Millet, V.
Hoyos, H.C.
Giannoni, J.P.
Croci, D.O.
Marder, M.
Liu, F.T.
Rabinovich, G.A.
Pasquini, J.M.
author_facet Pasquini, L.A.
Millet, V.
Hoyos, H.C.
Giannoni, J.P.
Croci, D.O.
Marder, M.
Liu, F.T.
Rabinovich, G.A.
Pasquini, J.M.
author_sort Pasquini, L.A.
title Galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function
title_short Galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function
title_full Galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function
title_fullStr Galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function
title_full_unstemmed Galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function
title_sort galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function
publishDate 2011
url http://hdl.handle.net/20.500.12110/paper_13509047_v18_n11_p1746_Pasquini
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