Molecular and cellular basis of radiation fibrosis.
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.
Burger
A
A
Department of Radiotherapy, Eberhard-Karls-University Tübingen, Germany.
Löffler
H
H
Bamberg
M
M
Rodemann
H P
HP
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*
D000906:Antibodies; D016212:Transforming Growth Factor beta