Brown, Robert A., Sethi, Kamaljit K., Gwanmesia, I., Raemdonck, D., 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 0014-4827Full text not available from this repository.
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.
|Additional Information:||Online ISSN 1090-2422|
|Uncontrolled Keywords:||Culture force monitor, transforming growth factor-Î², 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|
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