Expression of integrin ?1 by fibroblasts is required for tissue repair in vivo

Liu, Shangxi, Shi-Wen , Xu, Blumbach, Katrin, Eastwood, Mark, Denton, Christopher P., Eckes, Beate, Krieg, Thomas, Abraham, David J. and Leask, Andrew (2010) Expression of integrin ?1 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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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 ?1 exhibit delayed cutaneous wound closure and less granulation tissue formation, including reduced production of new ECM and reduced expression of ?-smooth muscle actin (?-SMA). Integrin-?1-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 ?-SMA stress fiber formation. Loss of integrin ?1 in adult fibroblasts reduced their ability to adhere to, to spread on and to contract ECM. Within stressed collagen matrices, integrin-?1-deficient fibroblasts showed reduced activation of latent TGF?. Addition of active TGF? alleviated the phenotype of integrin-?1-deficient mice. Thus integrin ?1 is essential for normal wound healing, where it acts, at least in part, through a TGF?-dependent mechanism in vivo.

Item Type: Article
Subjects: University of Westminster > Science and Technology > Life Sciences, School of (No longer in use)
Depositing User: Rachel Wheelhouse
Date Deposited: 23 Oct 2012 12:58
Last Modified: 23 Oct 2012 12:59

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