TGF-?1 decreases microglia-mediated neuroinflammation and lipid droplet accumulation in an in vitro stroke model

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dc.authorid0000-0002-1222-9211
dc.contributor.authorXin, Wenqiang
dc.contributor.authorPan, Yongli
dc.contributor.authorWei, Wei
dc.contributor.authorGerner, Stefan T.
dc.contributor.authorHuber, Sabine
dc.contributor.authorJuenemann, Martin
dc.contributor.authorButz, Marius
dc.contributor.authorBaehr, Mathias
dc.contributor.authorHuttner, Hagen B.
dc.contributor.authorDoeppner, Thorsten Roland
dc.date.accessioned2024-01-12T13:05:56Z
dc.date.available2024-01-12T13:05:56Z
dc.date.issued2023
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Sağlık Bilim ve Teknolojileri Araştırma Enstitüsü
dc.description.abstractHypoxia triggers reactive microglial inflammation and lipid droplet (LD) accumulation under stroke conditions, although the mutual interactions between these two processes are insufficiently understood. Hence, the involvement of transforming growth factor (TGF)-beta 1 in inflammation and LD accumulation in cultured microglia exposed to hypoxia were analyzed herein. Primary microglia were exposed to oxygen-glucose deprivation (OGD) injury and lipopolysaccharide (LPS) stimulation. For analyzing the role of TGF-beta 1 patterns under such conditions, a TGF-beta 1 siRNA and an exogenous recombinant TGF-beta 1 protein were employed. Further studies applied Triacsin C, an inhibitor of LD formation, in order to directly assess the impact of LD formation on the modulation of inflammation. To assess mutual microglia-to-neuron interactions, a co-culture model of these cells was established. Upon OGD exposure, microglial TGF-beta 1 levels were significantly increased, whereas LPS stimulation yielded decreased levels. Elevating TGF-beta 1 expression proved highly effective in suppressing inflammation and reducing LD accumulation in microglia exposed to LPS. Conversely, inhibition of TGF-beta 1 led to the promotion of microglial cell inflammation and an increase in LD accumulation in microglia exposed to OGD. Employing the LD formation inhibitor Triacsin C, in turn, polarized microglia towards an anti-inflammatory phenotype. Such modulation of both microglial TGF-beta 1 and LD levels significantly affected the resistance of co-cultured neurons. This study provides novel insights by demonstrating that TGF-beta 1 plays a protective role against microglia-mediated neuroinflammation through the suppression of LD accumulation. These findings offer a fresh perspective on stroke treatment, suggesting the potential of targeting this pathway for therapeutic interventions.
dc.description.sponsorshipChina Scholarship Councilen_US
dc.identifier.citationXin, W., Pan, Y., Wei, W., Gerner, S. T., Huber, S., Juenemann, M. ... Doeppner, T. R. (2023). TGF-?1 decreases microglia-mediated neuroinflammation and lipid droplet accumulation in an in vitro stroke model. International Journal of Molecular Sciences, 24(24). https://dx.doi.org/10.3390/ijms242417329
dc.identifier.doi10.3390/ijms242417329
dc.identifier.issn1661-6596
dc.identifier.issn1422-0067
dc.identifier.issue24
dc.identifier.pmid38139158
dc.identifier.scopus2-s2.0-85180645665
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://dx.doi.org/10.3390/ijms242417329
dc.identifier.urihttps://hdl.handle.net/20.500.12511/12135
dc.identifier.volume24
dc.identifier.wos001132258100001en_US
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorDoeppner, Thorsten Roland
dc.language.isoen
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)
dc.relation.ispartofInternational Journal of Molecular Sciencesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsAttribution 4.0 International*
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectInflammation
dc.subjectLipid Droplet
dc.subjectLipopolysaccharide
dc.subjectMicroglia
dc.subjectOxygen-Glucose Deprivation
dc.subjectStroke
dc.subjectTGF-?1
dc.titleTGF-?1 decreases microglia-mediated neuroinflammation and lipid droplet accumulation in an in vitro stroke model
dc.typeArticle

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