Expression of integrin β1 by fibroblasts is required for tissue repair in vivo

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 beta 1 exhibit delayed cutaneous wound closure and less granulation tissue formation, including reduced production of new ECM and reduced expression of alpha-smooth muscle actin (alpha-SMA). Integrin-beta 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 alpha-SMA stress fiber formation. Loss of integrin beta 1 in adult fibroblasts reduced their ability to adhere to, to spread on and to contract ECM. Within stressed collagen matrices, integrin-beta 1-deficient fibroblasts showed reduced activation of latent TGF beta. Addition of active TGF beta alleviated the phenotype of integrin-beta 1-deficient mice. Thus integrin beta 1 is essential for normal wound healing, where it acts, at least in part, through a TGF beta-dependent mechanism in vivo.