@phdthesis{oai:fdc.repo.nii.ac.jp:00000007,
 author = {Hata, Shozaburo and Okamura, Kazuhiko and Hatta, Mitsutoki and Ishikawa, Hiroyuki and Yamazaki, Jun},
 month = {2014-08-20, 2014-04-28, 2014-04-28},
 note = {2013年度, 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.},
 school = {福岡歯科大学},
 title = {Proteolytic and non-proteolytic activation of keratinocyte-derived latent TGF-β1 induces fibroblast differentiation in a wound-healing model using rat skin.},
 year = {}
}