title: Molecular and cellular basis of radiation fibrosis.
abstract: OBJECTIVE
  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.
  
  
  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.affiliation: Department of Radiotherapy, Eberhard-Karls-University Tübingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Burger
authors.forename: H
authors.initials: H
authors.lastname: Löffler
authors.forename: M
authors.initials: M
authors.lastname: Bamberg
authors.forename: H P
authors.initials: HP
authors.lastname: Rodemann
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D010641:Phenotype; D017564:Radiation Pneumonitis / Q000209:etiology* / Q000473:pathology; D051381:Rats; D013234:Stem Cells / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D016212:Transforming Growth Factor beta