Proteolytic and non-proteolytic activation of keratinocyte-derived latent TGF-β1 induces fibroblast differentiation in a wound-healing model using rat skin.

• Material Type: 博士論文
• Title: Proteolytic and non-proteolytic activation of keratinocyte-derived latent TGF-β1 induces fibroblast differentiation in a wound-healing model using rat skin.
• Author/Editor: Hata, Shozaburo; Okamura, Kazuhiko; Hatta, Mitsutoki; Ishikawa, Hiroyuki; Yamazaki, Jun
• Author Heading: Hata, Shozaburo; Okamura, Kazuhiko; Hatta, Mitsutoki; Ishikawa, Hiroyuki; Yamazaki, Jun
• Publication Date: 2014-03-15
• Publication Date (W3CDTF): 2014-03-15
• Alternative Title: Proteolytic and non-proteolytic activation of keratinocyte-derived latent TGF-β1 induces fibroblast differentiation in a wound-healing model using rat skin.
• Degree grantor/type: 福岡歯科大学
• Date Granted: 2014-03-15
• Date Granted (W3CDTF): 2014-03-15
• Dissertation Number: 甲第253号
• Degree Type: 博士（歯学）
• Conferring No. (Dissertation): 甲第253号
• Text Language Code: eng
• Subject Heading: keratinocyte; fibroblast; transforming growth factor-β1; αv-integrin; matrix metalloproteinase
• Target Audience: 一般
• Note (General): Transforming growth factor-β1 (TGF-β1) reportedly causes the differentiation of fibroblasts to myofibroblasts during wound healing. We investigated the mechanism underlying the activation of latent TGF-β1 released by keratinocytes in efforts to identify promising pharmacological approaches for the prevention of hypertrophic scar formation. A three-dimensional collagen gel matrix culture was prepared using rat keratinocytes and dermal fibroblasts. Stratified keratinocytes promoted the TGF receptor-dependent increase in α-smooth muscle actin (α-SMA) immunostaining and mRNA levels in fibroblasts. Latent TGF-β1 was found to be localized suprabasally and secreted. α-SMA expression was inhibited by an anti-αv-integrin antibody and a matrix metalloproteinase (MMP) inhibitor, GM6001. In a two-dimensional fibroblast culture, α-SMA expression depended on the production of endogenous TGF-β1 and required αv-integrin or MMP for the response to recombinant latent TGF-β1. In keratinocyte-conditioned medium, MMP-dependent latent TGF-β1 secretion was detected. Applying this medium to the fibroblast culture enhanced α-SMA production. This effect was decreased by GM6001, the anti-αv-integrin antibody, or the preabsorption of latent TGF-β1. These results indicate that keratinocytes secrete latent TGF-β1, which is liberated to fibroblasts over distance and is activated to produce α-SMA with the aid of a positive-feedback loop. MMP inhibition was effective for targeting both keratinocytes and fibroblasts in this model.; J Pharmacol Sci. 2014;124(2):230-43. Epub 2014 Jan 31.; J-STAGE
• Persistent ID (NDL): info:ndljp/pid/9479187; https://dl.ndl.go.jp/pid/9479187
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2015-08-01T14:40:15+09:00
• Date Created (W3CDTF): 2014-04-28
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Original Material (URI): J Pharmacol Sci. 2014;124(2):230-43. Epub 2014 Jan 31.; https://www.jstage.jst.go.jp/article/jphs/124/2/124_13209FP/_article
• Periodical Title (URI): https://fdc.repo.nii.ac.jp/records/7
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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