Liu, Shangxi and Shi-Wen , Xu and Blumbach, Katrin and Eastwood, Mark and Denton, Christopher P. and Eckes, Beate and Krieg, Thomas and Abraham, David J. and Leask, Andrew (2010) Expression of integrin β1 by fibroblasts is required for tissue repair in vivo. Journal of Cell Science, 123 (21). pp. 3674-3682. ISSN 0021-9533
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Official URL: http://dx.doi.org/10.1242/jcs.070672
In tissue repair, fibroblasts migrate into the wound to produce and remodel extracellular matrix (ECM). Integrins are believed to be crucial for tissue repair, but their tissue-specific role in this process is poorly understood. Here, we show that mice containing a fibroblast-specific deletion of integrin β1 exhibit delayed cutaneous wound closure and less granulation tissue formation, including reduced production of new ECM and reduced expression of α-smooth muscle actin (α-SMA). Integrin-β1-deficient fibroblasts showed reduced expression of type I collagen and connective tissue growth factor, and failed to differentiate into myofibroblasts as a result of reduced α-SMA stress fiber formation. Loss of integrin β1 in adult fibroblasts reduced their ability to adhere to, to spread on and to contract ECM. Within stressed collagen matrices, integrin-β1-deficient fibroblasts showed reduced activation of latent TGFβ. Addition of active TGFβ alleviated the phenotype of integrin-β1-deficient mice. Thus integrin β1 is essential for normal wound healing, where it acts, at least in part, through a TGFβ-dependent mechanism in vivo.
|Research Community:||University of Westminster > Life Sciences, School of|
|Deposited On:||23 Oct 2012 13:58|
|Last Modified:||23 Oct 2012 13:59|
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