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Permalink : http://id.nii.ac.jp/1167/00000003/
Proteolytic and non-proteolytic activation of keratinocyte-derived latent TGF-β1 induces fibroblast differentiation in a wound-healing model using rat skin.
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| アイテムタイプ | 学位論文 / Thesis or Dissertation |
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| 言語 | 英語 |
| キーワード |
keratinocyte, fibroblast, transforming growth factor-β1, αv-integrin, matrix metalloproteinase |
| 著者 |
Hata Shozaburo
Okamura Kazuhiko Hatta Mitsutoki Ishikawa Hiroyuki Yamazaki Jun |
| 抄録 |
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.
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| 学位名 |
博士（歯学）
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| 学位授与大学 |
福岡歯科大学
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| 学位授与年度 |
2013年度
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| 学位授与年月日 |
2014-03-15
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| 報告番号 |
37114甲第253号
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| 情報源 |
J Pharmacol Sci. 2014;124(2):230-43. Epub 2014 Jan 31.
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| 関連サイト |
J-STAGE
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| 著者版フラグ | ETD |
