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

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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:	JOUR
Materias:	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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_13509047_v18_n11_p1746_Pasquini
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_13509047_v18_n11_p1746_Pasquini2023-10-03T16:10:03Z Galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function 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. JOUR 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)
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	JOUR
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
url	http://hdl.handle.net/20.500.12110/paper_13509047_v18_n11_p1746_Pasquini
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_version_	1782023746591129600

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

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