Persistence of TGF-beta1 induction of increased fibroblast contractility.
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.
Liu
X D
XD
University of Nebraska Medical Center, Omaha 68198-5300, USA.
Umino
T
T
Ertl
R
R
Veys
T
T
Skold
C M
CM
Takigawa
K
K
Romberger
D J
DJ
Spurzem
J R
JR
Zhu
Y K
YK
Kohyama
T
T
Wang
H
H
Rennard
S I
SI
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
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