Enhanced fibroblast contraction of 3D collagen lattices and integrin expression by TGF-?1 and -?: mechanoregulatory growth factors?

Brown, Robert A. and Sethi, Kamaljit K. and Gwanmesia, I. and Raemdonck, D. and Eastwood, Mark and Mudera, Vivek (2002) Enhanced fibroblast contraction of 3D collagen lattices and integrin expression by TGF-?1 and -?: mechanoregulatory growth factors? Experimental Cell Research, 274 (2). pp. 310-322. ISSN 0014-4827

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Official URL: http://dx.doi.org/10.1006/excr.2002.5471


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-?s (TGF-?) 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-?1 and -?3 on contractile forces generated by human dermal fibroblasts. Maximal stimulation was between 7.5 and 15 ng/ml of TGF-?1. 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-?3 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-? might act through cell attachment and integrin function and the effect of TFG-? on expression of fibronectin (FnR) and vitronectin (VnR) integrin receptors was monitored over the same time scale. TGF-?1 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-?1 and -?3 behave here primarily as mechanoregulatory growth factors and that stimulation of integrin expression may be a consequence of the altered cell stress.

Item Type: Article
Additional Information: Online ISSN 1090-2422
Uncontrolled Keywords: Culture force monitor, transforming growth factor-β, human dermal fibroblasts; collagen lattices; force generation; cytomechanics, fibronectin, vitronectin, integrins
Subjects: University of Westminster > Science and Technology > Life Sciences, School of (No longer in use)
Depositing User: Users 4 not found.
Date Deposited: 01 Dec 2005
Last Modified: 02 Jul 2008 11:43
URI: http://westminsterresearch.wmin.ac.uk/id/eprint/253

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