title: Persistence of TGF-beta1 induction of increased fibroblast contractility.
abstract: Fibroblast contraction of collagen gels is regarded as a model of wound contraction. Transforming growth factor (TGF)-beta added to such gels can augment contraction consistent with its suggested role as a mediator of fibrotic repair. Since fibroblasts isolated from fibrotic tissues have been suggested to express a "fibrotic phenotype," we hypothesized that TGF-beta exposure may lead to a persistent increase in fibroblasts' contractility. To evaluate this question, confluent human fetal lung fibroblasts were treated with serum-free Dulbecco modified Eagle medium (DMEM), with or without 100 pM [corrected] TGF-beta1, TGF-beta2, or TGF-beta3 for 48 h. Fibroblasts were then trypsinized and cast into gels composed of native type I collagen isolated from rat tail tendons. After 20 min for gelation, the gels were released and maintained in serum-free DMEM. TGF-beta-pretreated fibroblasts caused significantly more rapid gel contraction (52.5+/-0.6, 50.9+/-0.2, and 50.3+/-0.5% by TGF-beta1, -beta2, and -beta3 pretreated fibroblasts, respectively) than control fibroblasts (74.0+/-0.3%, P < 0.01). This effect is concentration dependent (50-200 nM), and all three isoforms had equal activity. The effect of TGF-beta1, however, persisted for only a short period of time following the removal of TGF-beta, and was lost with sequential passage. These observations suggest that the persistent increase in collagen-gel contractility, mediated by fibroblasts from fibrotic tissues, would not appear to be solely due to previous exposure of these cells to TGF-beta.
authors.affiliation: University of Nebraska Medical Center, Omaha 68198-5300, USA.
authors.forename: X D
authors.initials: XD
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Umino
authors.forename: R
authors.initials: R
authors.lastname: Ertl
authors.forename: T
authors.initials: T
authors.lastname: Veys
authors.forename: C M
authors.initials: CM
authors.lastname: Skold
authors.forename: K
authors.initials: K
authors.lastname: Takigawa
authors.forename: D J
authors.initials: DJ
authors.lastname: Romberger
authors.forename: J R
authors.initials: JR
authors.lastname: Spurzem
authors.forename: Y K
authors.initials: YK
authors.lastname: Zhu
authors.forename: T
authors.initials: T
authors.lastname: Kohyama
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: S I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: D000328:Adult; D000818:Animals; D001980:Bronchi / Q000166:cytology; D002452:Cell Count; D002460:Cell Line; D048429:Cell Size; D003094:Collagen / Q000032:analysis; D003550:Cystic Fibrosis / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D005782:Gels; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000196:embryology; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3
chemical_list: D005782:Gels; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; C508962:Tgfb1 protein, rat; C509046:Tgfb3 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D003094:Collagen