Persistence of TGF-beta 1 induction of increased fibroblast contractility

Fibroblast contraction of collagen gels is regarded as a model of wound con traction. Transforming growth factor (TGF)-beta added to such gels can augm ent contraction consistent with its suggested role as a mediator of fibroti c repair. Since fibroblasts isolated from fibrotic tissues have been sugges ted to express a "fibrotic phenotype," we hypothesized that TGF-beta exposu re may lead to a persistent increase in fibroblasts' contractility. To eval uate this question, confluent human fetal lung fibroblasts were treated wit h serum-free Dulbecco modified Eagle medium (DMEM), with or without 100 nM TGF-beta1, TGF-beta2, or TGF-beta3 for 48 h. Fibroblasts were then trypsini zed and cast into gels composed of native type I collagen isolated from rat tail tendons. After 20 min fbr gelation, the gels were released and mainta ined in serum-free DMEM. TGF-beta -pretreated fibroblasts caused significan tly 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) t han control fibroblasts (74.0 +/- 0.3%, P < 0.01). This effect is concentra tion dependent (50-200 nM), and all three isoforms had equal activity. The effect of TGF-<beta>1, however, persisted for only a short period of time f ollowing the removal of TGF-beta, and was lost with sequential passage. The se observations suggest that the persistent increase in collagen-gel contra ctility mediated hy fibroblasts from fibrotic tissues, would not appear to he solely due to previous exposure of these cells to TGF-beta.