| Item type |
学位論文 / Thesis or Dissertation(1) |
| 公開日 |
2014-04-28 |
| タイトル |
|
|
タイトル |
Proteolytic and non-proteolytic activation of keratinocyte-derived latent TGF-β1 induces fibroblast differentiation in a wound-healing model using rat skin. |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| キーワード |
|
|
言語 |
en |
|
主題 |
keratinocyte |
| キーワード |
|
|
言語 |
en |
|
主題 |
fibroblast |
| キーワード |
|
|
言語 |
en |
|
主題 |
transforming growth factor-β1 |
| キーワード |
|
|
言語 |
en |
|
主題 |
αv-integrin |
| キーワード |
|
|
言語 |
en |
|
主題 |
matrix metalloproteinase |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
|
資源タイプ |
doctoral thesis |
| 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 |
| 著者 |
Hata, Shozaburo
Okamura, Kazuhiko
Hatta, Mitsutoki
Ishikawa, Hiroyuki
Yamazaki, Jun
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
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. |
| 学位名 |
|
|
学位名 |
博士（歯学） |
| 学位授与大学 |
|
|
|
学位授与機関識別子 |
37114 |
|
|
学位授与機関名 |
福岡歯科大学 |
| 学位授与年度 |
|
|
内容記述 |
2013年度 |
| 学位授与年月日 |
|
|
学位授与年月日 |
2014-03-15 |
| 報告番号 |
|
|
学位授与番号 |
甲第253号 |
| 情報源 |
|
|
|
関連名称 |
J Pharmacol Sci. 2014;124(2):230-43. Epub 2014 Jan 31. |
| 関連サイト |
|
|
|
識別子タイプ |
URI |
|
|
関連識別子 |
https://www.jstage.jst.go.jp/article/jphs/124/2/124_13209FP/_article |
|
|
関連名称 |
J-STAGE |
| 著者版フラグ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
甲第253号_論文(秦) (5.9 MB)
