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Reduced FOXO1 Expression Accelerates Skin Wound Healing and Attenuates Scarring
http://hdl.handle.net/10069/34774
http://hdl.handle.net/10069/34774f1ace77e-90e0-4e29-a6db-4f7f0d1b5704
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Supple_Data.pdf (904.4 kB)
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TAJP184_2465.pdf (2.4 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2014-10-14 | |||||
タイトル | ||||||
タイトル | Reduced FOXO1 Expression Accelerates Skin Wound Healing and Attenuates Scarring | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Mori, Ryoichi
× Mori, Ryoichi× Tanaka, Katsuya× de, Kerckhove Maiko× Okamoto, Momoko× Kashiyama, Kazuya× Tanaka, Katsumi× Kim, Sangeun× Kawata, Takuya× Komatsu, Toshimitsu× Park, Seongjoon× Ikematsu, Kazuya× Hirano, Akiyoshi× Martin, Paul× Shimokawa, Isao |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1 +/- mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a-/- mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1+/- mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring. | |||||
書誌情報 |
The American Journal of Pathology 巻 184, 号 9, p. 2465-2479, 発行日 2014-09 |
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出版者 | ||||||
出版者 | Elsevier Inc. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 00029440 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.ajpath.2014.05.012 | |||||
権利 | ||||||
権利情報 | c 2014 American Society for Investigative Pathology. Published by Elsevier Inc. | |||||
権利 | ||||||
権利情報 | NOTICE: this is the author’s version of a work that was accepted for publication in American Journal of Pathology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in American Journal of Pathology, 184, 9, (2014) | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | The American Journal of Pathology, 184(9), pp.2465-2479; 2014 |