Transforming growth factor-β stimulates β amyloid uptake by microglia through Smad3-dependent mechanisms

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dc.contributor.authorTichauer, Juan E.
dc.contributor.authorvon Bernhardi, Rommy
dc.date.accessioned2025-01-20T23:56:58Z
dc.date.available2025-01-20T23:56:58Z
dc.date.issued2012
dc.description.abstractInflammatory cytokines and beta amyloid (A beta) induce activation of glial cells, leading to both protective and deleterious changes that are relevant for the pathogenesis of Alzheimer disease (AD). We have shown that astrocytes downregulate microglial cell cytotoxic activation through secretion of transforming growth factor-beta (TGF beta 1), and there is evidence that TGF beta 1 modifies A beta removal through the modulation of microglia. However, inflammatory activation of microglia is increased and A beta clearance is reduced in AD patients, regardless of the fact that TGF beta 1 is increased in their nervous system. We propose that changes in TGF beta Smad3 signal transduction could modify the regulation mediated by TGF beta 1. Here we evaluated the participation of the TGF beta Smad3 pathway in regulation of the expression pattern of scavenger receptors (SR) and activation of microglia through nitric oxide (NO.) secretion and phagocytosis of A beta. We found that TGF beta 1 increased SR-A by 2.4-fold and decreased SR-BI expression by 79% at 48 hr, whereas it did not change SR-MARCO or CD36 expression. In addition, we observed a 51% increase of A beta uptake and an 83% decrease of NO. production induced by lipopolysaccharide in microglial cell cultures. Increased expression of SR-A, phagocytosis, and downregulation of NO. by TGF beta 1 were prevented by the inhibition of the TGF beta Smad3 pathway. Our results indicate that the modulation of microglial cell activation by TGF beta 1, leading to increased clearance of A beta and reduced cytotoxicity, is at least partially mediated by the Smad pathway. (c) 2012 Wiley Periodicals, Inc.
dc.fuente.origenWOS
dc.identifier.doi10.1002/jnr.23082
dc.identifier.eissn1097-4547
dc.identifier.issn0360-4012
dc.identifier.urihttps://doi.org/10.1002/jnr.23082
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/95182
dc.identifier.wosidWOS:000307383800011
dc.issue.numero10
dc.language.isoen
dc.pagina.final1980
dc.pagina.inicio1970
dc.revistaJournal of neuroscience research
dc.rightsacceso restringido
dc.subjectAlzheimer's disease
dc.subjectcytokines
dc.subjectglia
dc.subjectneuroinflammation
dc.subjectSR-A
dc.subjecttransforming growth factor-ss
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleTransforming growth factor-β stimulates β amyloid uptake by microglia through Smad3-dependent mechanisms
dc.typeartículo
dc.volumen90
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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