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High Mobility Group Box 1 as an Autocrine Chemoattractant for Oligodendrocyte Lineage Cells in White Matter Stroke

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dc.contributor.authorChoi, JY-
dc.contributor.authorJin, X-
dc.contributor.authorKim, H-
dc.contributor.authorKoh, S-
dc.contributor.authorCho, HJ-
dc.contributor.authorKim, BG-
dc.date.accessioned2023-05-23T04:04:16Z-
dc.date.available2023-05-23T04:04:16Z-
dc.date.issued2023-
dc.identifier.issn0039-2499-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/25530-
dc.description.abstractBackground: The migration of oligodendrocyte precursor cells (OPC) is a key process of remyelination, which is essential for the treatment of white matter stroke. This study aimed to investigate the role of HMGB1 (high mobility group box 1), a damage-associated molecular pattern released from dying oligodendrocytes, as an autocrine chemoattractant that promotes OPC migration. Methods: The migratory capacity of primary cultured OPCs was measured using the Boyden chamber assay. The downstream pathway of HMGB1-mediated OPC migration was specified by siRNA-induced knockdown or pharmacological blockade of TLR2 (toll-like receptor 2), RAGE (receptor for advanced glycation end product), Src, ERK1/2 (extracellular signal-regulated kinase1/2), and FAK (focal adhesion kinase). Conditioned media were collected from oxygen-glucose deprivation-treated oligodendrocytes, and the impact on OPC migration was assessed. Lesion size and number of intralesional Olig2(+) cells were analyzed in an in vivo model of white matter stroke with N5-(1-iminoethyl)-L-ornithine (L-NIO). Results: HMGB1 treatment promoted OPC migration. HMGB1 antagonism reversed such effects to untreated levels. Among the candidates for the downstream signal of HMGB1-mediated migration, the knockdown of TLR2 rather than that of RAGE attenuated the migration-promoting effect of HMGB1. Further specification of the HMGB1-TLR2 axis revealed that the phosphorylation of ERK1/2 and its downstream molecule FAK, rather than of Src, was decreased in TLR2-knockdown OPCs, and pharmacological inhibition of ERK1/2 and FAK led to decreased OPC migration. Oxygen-glucose deprivation-conditioned media promoted OPC migration, suggesting the autocrine chemoattractant function of HMGB1. In vivo, TLR2(-/-)-mice showed lesser intralesional Olig2(+) cells compared to wild-type controls in response to L-NIO induced ischemic injury regardless of HMGB1 administration. Conclusions: HMGB1, through the TLR2-ERK1/2-FAK axis, functions as an autocrine chemoattractant to promote OPC migration, which is an initial and indispensable step in remyelination. Thus, a novel treatment strategy for white matter stroke based on the HMGB1-TLR2 axis in the oligodendrocyte lineage could be feasible.-
dc.language.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHCell Lineage-
dc.subject.MESHCulture Media, Conditioned-
dc.subject.MESHHMGB1 Protein-
dc.subject.MESHMice-
dc.subject.MESHOligodendroglia-
dc.subject.MESHStroke-
dc.subject.MESHToll-Like Receptor 2-
dc.subject.MESHWhite Matter-
dc.titleHigh Mobility Group Box 1 as an Autocrine Chemoattractant for Oligodendrocyte Lineage Cells in White Matter Stroke-
dc.typeArticle-
dc.identifier.pmid36490365-
dc.subject.keywordinternal capsule-
dc.subject.keywordischemic stroke-
dc.subject.keywordmicroglia-
dc.subject.keywordoligodendroglia-
dc.subject.keywordwhite matter-
dc.contributor.affiliatedAuthorChoi, JY-
dc.contributor.affiliatedAuthorKoh, S-
dc.contributor.affiliatedAuthorKim, BG-
dc.type.localJournal Papers-
dc.identifier.doi10.1161/STROKEAHA.122.041414-
dc.citation.titleStroke-
dc.citation.volume54-
dc.citation.number2-
dc.citation.date2023-
dc.citation.startPage575-
dc.citation.endPage586-
dc.identifier.bibliographicCitationStroke, 54(2). : 575-586, 2023-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn1524-4628-
dc.relation.journalidJ000392499-
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Journal Papers > School of Medicine / Graduate School of Medicine > Brain Science
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