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Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Promote Recovery after Rat Spinal Cord Injury by Altering Macrophage Polarity
http://hdl.handle.net/2237/25433
http://hdl.handle.net/2237/254338acaaa8e-c1a9-46a5-a83d-0d4132620a01
名前 / ファイル | ライセンス | アクション |
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2452_full.pdf (6.0 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-01-19 | |||||
タイトル | ||||||
タイトル | Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Promote Recovery after Rat Spinal Cord Injury by Altering Macrophage Polarity | |||||
言語 | en | |||||
著者 |
Matsubara, Kohki
× Matsubara, Kohki× Matsushita, Yoshihiro× Sakai, Kiyoshi× Kano, Fumiya× Kondo, Megumi× Noda, Mariko× Hashimoto, Noboru× Imagama, Shiro× Ishiguro, Naoki× Suzumura, Akio× Ueda, Minoru× Furukawa, Koichi× Yamamoto, Akihito |
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アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
権利 | ||||||
言語 | en | |||||
権利情報 | Copyright(c)2015 the authors | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | anti-inflammation | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | dental pulp stem cells | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | macrophage polarity | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | MCP-1 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Siglec-9 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | spinal cord injury | |||||
抄録 | ||||||
内容記述 | Engrafted mesenchymal stem cells from human deciduous dental pulp (SHEDs) support recovery from neural insults via paracrine mechanisms that are poorly understood. Here we show that the conditioned serum-free medium (CM) from SHEDs, administered intrathecally into rat injured spinal cord during the acute postinjury period, caused remarkable functional recovery. The ability of SHED-CM to induce recovery was associated with an immunoregulatory activity that induced anti-inflammatory M2-like macrophages. Secretome analysis of the SHED-CM revealed a previously unrecognized set of inducers for anti-inflammatory M2-like macrophages: monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9). Depleting MCP-1 and ED-Siglec-9 from the SHED-CM prominently reduced its ability to induce M2-like macrophages and to promote functional recovery after spinal cord injury (SCI). The combination of MCP-1 and ED-Siglec-9 synergistically promoted the M2-like differentiation of bone marrow-derived macrophages in vitro, and this effect was abolished by a selective antagonist for CC chemokine receptor 2 (CCR2) or by the genetic knock-out of CCR2. Furthermore, MCP-1 and ED-Siglec-9 administration into the injured spinal cord induced M2-like macrophages and led to a marked recovery of hindlimb locomotor function after SCI. The inhibition of this M2 induction through the inactivation of CCR2 function abolished the therapeutic effects of both SHED-CM and MCP-1/ED-Siglec-9. Macrophages activated by MCP-1 and ED-Siglec-9 extended neurite and suppressed apoptosis of primary cerebellar granule neurons against the neurotoxic effects of chondroitin sulfate proteoglycans. Our data suggest that the unique combination of MCP-1 and ED-Siglec-9 repairs the SCI through anti-inflammatory M2-like macrophage induction. | |||||
言語 | en | |||||
内容記述タイプ | Abstract | |||||
出版者 | ||||||
言語 | en | |||||
出版者 | Society for Neuroscience | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプresource | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
出版タイプ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1523/JNEUROSCI.4088-14.2015 | |||||
ISSN | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 0270-6474 | |||||
書誌情報 |
en : The Journal of Neuroscience 巻 35, 号 6, p. 2452-2464, 発行日 2015-02 |
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著者版フラグ | ||||||
値 | publisher | |||||
URI | ||||||
識別子 | https://doi.org/10.1523/JNEUROSCI.4088-14.2015 | |||||
識別子タイプ | DOI | |||||
URI | ||||||
識別子 | http://hdl.handle.net/2237/25433 | |||||
識別子タイプ | HDL |