|Title||Enhanced fibroblast contraction of 3D collagen lattices and integrin expression by TGF-β1 and -β: mechanoregulatory growth factors?|
|Authors||Brown, R.A., Sethi, K.K., Gwanmesia, I., Raemdonck, D., Eastwood, M. and Mudera, V.|
Generation of contractile forces as fibroblasts attach and migrate through collagenous substrates is a fundamental behavior, yet its regulation and consequences are obscure. Although the transforming growth factor-βs (TGF-β) are similarly important in fibrosis and tissue repair, their role in contraction is controversial. Using a quantitative, 3D collagen culture model we have measured the effects of TGF-β1 and -β3 on contractile forces generated by human dermal fibroblasts. Maximal stimulation was between 7.5 and 15 ng/ml of TGF-β1. Higher doses were inhibitory (30 ng/ml), giving a bell-shaped dose response. The initial rate of force generation was increased sevenfold (15 ng/ml). A similar response pattern was seen with TGF-β3 alone. However, the addition of both isoforms together stimulated a biphasic increase in force generation, suggesting that there was a distinct temporal cooperativity between the two isforms. This very early onset (10–20 min) of stimulation suggested that TGF-β might act through cell attachment and integrin function and the effect of TFG-β on expression of fibronectin (FnR) and vitronectin (VnR) integrin receptors was monitored over the same time scale. TGF-β1 dramatically up-regulated VnR expression, relative to FnR, over time but the optimal time for this was 2–4 h later than that of force stimulation. It is concluded that TGF-β1 and -β3 behave here primarily as mechanoregulatory growth factors and that stimulation of integrin expression may be a consequence of the altered cell stress.
|Keywords||Culture force monitor, transforming growth factor-Î², human dermal fibroblasts; collagen lattices; force generation; cytomechanics, fibronectin, vitronectin, integrins|
|Journal||Experimental Cell Research|
|Journal citation||274 (2), pp. 310-322|
|Digital Object Identifier (DOI)||doi:10.1006/excr.2002.5471|