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A 3D epithelial-mesenchymal co-culture model of human bronchial tissue recapitulates multiple features of airway tissue remodeling by TGF-ß1 treatment.
Ishikawa, Shinkichi; Ishimori, Kanae; Ito, Shigeaki.
Afiliação
  • Ishikawa S; Scientific Product Assessment Center, R&D Group, Japan Tobacco Inc., 6-2 Umegaoka, Aoba-ku, Yokohama, Kanagawa, 227-8512, Japan. shinkichi.ishikawa@jt.com.
  • Ishimori K; Scientific Product Assessment Center, R&D Group, Japan Tobacco Inc., 6-2 Umegaoka, Aoba-ku, Yokohama, Kanagawa, 227-8512, Japan.
  • Ito S; Scientific Product Assessment Center, R&D Group, Japan Tobacco Inc., 6-2 Umegaoka, Aoba-ku, Yokohama, Kanagawa, 227-8512, Japan.
Respir Res ; 18(1): 195, 2017 11 22.
Article em En | MEDLINE | ID: mdl-29166920
BACKGROUND: The collagen gel contraction assay measures gel size to assess the contraction of cells embedded in collagen gel matrices. Using the assay with lung fibroblasts is useful in studying the lung tissue remodeling process in wound healing and disease development. However, the involvement of bronchial epithelial cells in this process should also be investigated. METHODS: We applied a layer of mucociliary differentiated bronchial epithelial cells onto collagen gel matrices with lung fibroblasts. This co-culture model enables direct contact between epithelial and mesenchymal cells. We stimulated the culture with transforming growth factor (TGF) ß1 as an inducer of tissue remodeling for 21 days, and measured gel size, histological changes, and expression of factors related to extracellular matrix homeostasis. RESULTS: TGF-ß1 exerted a concentration-dependent effect on collagen gel contraction and on contractile myofibroblasts in the mesenchymal collagen layer. TGF-ß1 also induced expression of the mesenchymal marker vimentin in the basal layer of the epithelium, suggesting the induction of epithelial-mesenchymal transition. In addition, the expression of various genes encoding extracellular matrix proteins was upregulated. Fibrotic tenascin-C accumulated in the sub-epithelial region of the co-culture model. CONCLUSION: Our findings indicate that TGF-ß1 can affect both epithelial and mesenchymal cells, and induce gel contraction and structural changes. Our novel in vitro co-culture model will be a useful tool for investigating the roles of epithelial cells, fibroblasts, and their interactions in the airway remodeling process.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Mucosa Respiratória / Fator de Crescimento Transformador beta1 / Remodelação das Vias Aéreas / Transição Epitelial-Mesenquimal / Pulmão Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Mucosa Respiratória / Fator de Crescimento Transformador beta1 / Remodelação das Vias Aéreas / Transição Epitelial-Mesenquimal / Pulmão Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article