PURPOSE: Recent data from the literature and the experimental work of the authors clearly indicate that TGF-beta1 is a key modulator of cellular events, for example, induction of terminal differentiation, resulting in radiation-induced fibrosis. Therefore, the present study analysed which cellular processes induced by exogenously added TGF-beta could be responsible for the induction, development and manifestation of the fibrotic phenotype in culture. MATERIALS AND METHODS: Rat lung fibroblast cultures (passage 1) were used. As a function of treatment with TGF-beta and/or anti-TGF-beta-antibody, the clonogenic activity and differentiation pattern were analysed by colony-formation assays. RESULTS: It could be demonstrated that treatment of rat lung progenitor fibroblasts with TGF-beta1 resulted in a pronounced shift in the differentiation pattern, i.e. induction of post-mitotic fibrocytes. This TGF-beta1-dependent terminal differentiation could be abolished by simultaneous treatment with a neutralizing antibody directed against TGF-beta1. CONCLUSIONS: The data presented indicate that TGF-beta1 is one major candidate mediating the accelerated terminal differentiation of progenitor fibroblasts to post-mitotic functional fibrocytes, which results in the fibrotic phenotype of this cell system.
PURPOSE: Recent data from the literature and the experimental work of the authors clearly indicate that TGF-beta1 is a key modulator of cellular events, for example, induction of terminal differentiation, resulting in radiation-induced fibrosis. Therefore, the present study analysed which cellular processes induced by exogenously added TGF-beta could be responsible for the induction, development and manifestation of the fibrotic phenotype in culture. MATERIALS AND METHODS:Rat lung fibroblast cultures (passage 1) were used. As a function of treatment with TGF-beta and/or anti-TGF-beta-antibody, the clonogenic activity and differentiation pattern were analysed by colony-formation assays. RESULTS: It could be demonstrated that treatment of rat lung progenitor fibroblasts with TGF-beta1 resulted in a pronounced shift in the differentiation pattern, i.e. induction of post-mitotic fibrocytes. This TGF-beta1-dependent terminal differentiation could be abolished by simultaneous treatment with a neutralizing antibody directed against TGF-beta1. CONCLUSIONS: The data presented indicate that TGF-beta1 is one major candidate mediating the accelerated terminal differentiation of progenitor fibroblasts to post-mitotic functional fibrocytes, which results in the fibrotic phenotype of this cell system.
Authors: Jeffrey M Straub; Jacob New; Chase D Hamilton; Chris Lominska; Yelizaveta Shnayder; Sufi M Thomas Journal: J Cancer Res Clin Oncol Date: 2015-04-25 Impact factor: 4.553
Authors: R Ordoñez; L A Henríquez-Hernández; M Federico; A Valenciano; B Pinar; M Lloret; E Bordón; C Rodríguez-Gallego; P C Lara Journal: Strahlenther Onkol Date: 2013-12-22 Impact factor: 3.621